|Year : 2016 | Volume
| Issue : 2 | Page : 705-711
Quantification of oral palatine Langerhans cells in HIV/AIDS associated oral Kaposi sarcoma with and without oral candidiasis
Vibha Jivan, Shabnum Meer
Department of Oral Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
|Date of Web Publication||25-Jul-2016|
Department of Oral Pathology, Faculty of Health Sciences, Private Bag 3, World Integrated Trade Solution (WITS), 2050, Johannesburg
Source of Support: None, Conflict of Interest: None
Context: Langerhans cells (LCs) are effective antigen-presenting cells that function as “custodians” of mucosa, modifying the immune system to pathogen entry, and tolerance to self-antigen and commensal microbes. A reduction in number of LCs in human immunodeficiency virus (HIV)-positive individuals may predispose to local mucosal infections.
Aims: To quantitatively determine the number of oral mucosal LCs in HIV/acquired immunodeficiency syndrome HIV/acquired immunodeficiency syndrome (AIDS) associated oral Kaposi sarcoma (KS) with/without oral candidiasis (OC) and to define in situ interrelationships between the cells, OC, and HIV infection.
Materials and Methods: Thirty-two periodic acid-Schiff. (PAS) stained histologic sections of palatal HIV/AIDS associated KS with intact oral epithelium were examined for Candida and divided into two groups: . (1) KS coinfected with Candida and. (2) KS noninfected with Candida. Sections were immunohistochemically stained with CD1a. The standard length of surface epithelium was measured and number of positively stained LCs counted per unit length. Control cases included non-Candida infected palatal mucosa overlying pleomorphic adenoma. (PA) and oral mucosa infected with Candida in otherwise healthy individuals.
Results: LC number per unit length of surface epithelium was statistically significantly greatest in uninfected PA mucosa and lowest in KS coinfected with Candida (P = 0.0001). A statistically significant difference was also noted between uninfected PA mucosa and non-Candida infected KS (P = 0.0014), in KS coinfected with Candida and non-infected KS (P = 0.0035), between OC and PA (P = 0.0001), and OC and KS coinfected with Candida (P = 0.0247).
Conclusion: LC numbers are significantly reduced in oral tissues of HIV/AIDS infected patients by Candida infection when compared to oral tissues without.
Keywords: AIDS, HIV, kaposi sarcoma, oral candidiasis, oral Langerhans cells
|How to cite this article:|
Jivan V, Meer S. Quantification of oral palatine Langerhans cells in HIV/AIDS associated oral Kaposi sarcoma with and without oral candidiasis. J Can Res Ther 2016;12:705-11
|How to cite this URL:|
Jivan V, Meer S. Quantification of oral palatine Langerhans cells in HIV/AIDS associated oral Kaposi sarcoma with and without oral candidiasis. J Can Res Ther [serial online] 2016 [cited 2020 Jul 15];12:705-11. Available from: http://www.cancerjournal.net/text.asp?2016/12/2/705/148659
| > Introduction|| |
Langerhans cells (LCs) play a key role in mucosal homeostasis and immunity, recognizing and tolerating commensal microorganisms in noninflammatory conditions, and mediating immunoinflammatory reactions against pathogens.,, Oral mucosal LCs are sentinel in the response, amongst others to oral Candida, lichen planus, lichenoid drug reactions, human immunodeficiency virus (HIV) infection, hairy leukoplakia, and oral squamous cell carcinoma. This study aimed to quantitatively determine number of oral mucosal LCs in HIV/acquired immunodeficiency syndrome (AIDS) associated oral Kaposi sarcoma (KS) with/without oral candidiasis (OC) and to define in situ interrelationships between the cells, OC, and HIV infection, with a view to elucidate their role in pathogenesis and to determine a rationale for treatment strategies.
| > Materials and Methods|| |
Thirty-two consecutive cases of oral HIV/AIDS-associated KS diagnosed over a 2-year period were retrieved from the archives of the Department of Oral Pathology. All biopsy specimens were from palatal KS lesions from confirmed HIV/AIDS patients. The KS lesions were from the anterior palatine mucosa in the region of the maxillary incisor and canine teeth and ranged in size from about 2 × 1 × 1 mm to 20 × 15 × 15 mm. Only cases of KS with intact, nonulcerated overlying palatal epithelium were included. Data on whether patients were on highly active antiretroviral treatment (HAART), whether they showed any clinical evidence of OC, and patient CD4 + T-cell counts were not available.
Control groups comprised non-Candida infected palatal mucosa overlying pleomorphic adenomas (PAs; Control 1) and Candida infected oral mucosal cases in otherwise healthy individuals (OC; Control 2). Control 1 comprised 23 randomly selected cases of palatal PA with intact, nonulcerated overlying anterior palatal epithelium which were consecutively retrieved over the same 2-year period. All control cases were of confirmed HIV-seronegative patients with no Candida infection of overlying epithelium.
Control 2 comprised 19 cases of confirmed primary OC with no underlying oral pathology and was not Candida super infection of preexisting pathology. These cases included tissue biopsies from oral mucosal sites such as palate, tongue, and buccal mucosa in apparently healthy individuals. Even though it would have been ideal to use cases of palatal candidiasis as comparison, this was not possible as tissue of OC in otherwise healthy individuals was unavailable. This is due to OC often being a clinical diagnosis frequently confirmed with a noninvasive smear biopsy rather than a tissue biopsy. The ethics clearance number, M00/28/09 for this study was issued by the Human Research Ethics Committee (Medical) of the University of the Witwatersrand, for use of archival block material obtained from human tissues.
Histopathological and immunohistochemical analysis
Histologic sections of 32 cases of palatal KS with intact epithelium were stained with periodic acid-Schiff (PAS) and examined under light microscopy for the presence of Candida in two groups: (i) where surface epithelium showed no infection with Candida (KS − C) (n = 15) [Figure 1]a and (ii) where varying degrees of colonization by Candida microorganisms within surface epithelium was present (KS + C) (n = 17) [Figure 1]b and [Figure 1]c. A diagnosis of Candida infection was confirmed by tissue invasion of pseudohyphae into keratinous layers of palatine epithelium and not just superficial adherence by Candida pseudohyphae [Figure 1]c. Control 1 (PA) sections were from the same palatine mucosal area as study group lesions and were also stained with PAS to rule out Candida infection. Tissue sections of Control 2 (OC) were from oral mucosal sites as described with Candida infection confirmed with PAS stains.
|Figure 1: (a) Palatal Kaposi sarcoma (KS) showing no infection of surface epithelium with Candida (KS–C) (hematoxylin and eosin (H and E), original magnification × 400) and (b and c) varying degrees of colonization by Candida (KS–C) (periodic acid-Schiff (PAS), original magnification × 200 (b) and × 400 (c)). A diagnosis required tissue invasion by Candida pseudohyphae into keratinous layers of epithelium (c)|
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Immunohistochemistry was performed on deparaffinized 4 µm tissue sections of all cases (study and control) with monoclonal CD1a (DakoCytomation, Glostrup, Denmark). The tissue was previously fixed in 10% buffered formalin and processed for routine light microscopy and immunohistochemistry. Sections were placed on 3-aminopropyltriethoxysilane (APES, Sigma, St Louis, MO) glass slides, which were air-dried overnight, dewaxed, and hydrated through graded alcohols and water. Sections were then pretreated by heating in a microwave oven (800 W) on medium power for 10 min. For CD1a antibody epitope retrieval, tissue sections were microwaved in citrate buffer at pH 6.0, cooled for 20 min, and successfully incubated with primary monoclonal antibodies against CD1a (clone 010, 1:400 dilution; DakoCytomation). After incubation with primary antibody, secondary antibodies conjugated with streptavidin-biotin-peroxidase (K0690; Universal Dako LSAB + Kit, Peroxidase, Carpinteria, CA, USA) developed with diaminobenzidine and counterstained with Carazzi¢s hematoxylin, were used. Negative controls were performed for each reaction via omission of primary antibodies.
Dense brown nuclear staining was regarded as positive within LCs. Positively stained LCs in the epithelium were counted, using an eyepiece mounted ruler in order to measure a standardized length of surface epithelium, at a magnification of ×200 [Figure 2]. The standard length of surface epithelium was measured and number of positively stained LCs counted per unit length. For each case LCs in 5 unit lengths were counted and average number of LCs per case was calculated.
|Figure 2: Artist impression through microscope eye lens depicting examination field. An eyepiece mounted ruler was used to measure a standardized length of surface epithelium, at a magnification of × 200|
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Intra- and interexaminer reliability was established using a paired t-test. In order to accomplish this, the CD1a positive cells were counted in a representative number of sections by two different examiners and by the same examiner on two different occasions. Results were analyzed and statistically compared using an unpaired t-test. Probability levels of <5% were regarded as statistically significant.
| > Results|| |
The male:female ratio in total KS − C and KS + C study sample was 1:1.46 (13 males (40.63%) and 19 females (59.37%)). When considered separately, the male:female ratio was 1:1.13 (8 males (47.06%) and 9 females (52.94%)) and 1:2 (5 males (33.33%) and 10 females (66.67%)) in the KS − C (n = 17) and KS + C (n = 15) groups, respectively. The overall age for the entire study group ranged from 4 to 63 years (mean, 31.94; median, 33; and range, 59), and the age for KS − C group ranged from 4 to 63 years (mean, 33.56; median, 35; and range, 59) and KS + C group ranged from 21 to 45 years (mean, 32.36; median, 33; and range, 24).
Control 1 (PA) showed a male:female ratio of 1:1.3 (10 males (43.48%) and 13 females (56.52%)). Age ranged from 9 to 75 years (mean, 43.65; median, 40; and range, 66). Total number of patients in Control 2 (OC) was 16 as 3 patients with OC showed separate noncontiguous sites of involvement. This group showed a male:female ratio of 1.7:1 (10 males (62.50%) and 6 females (37.50%)). The age ranged from 36 to 93 years (mean, 61.38; median, 63.50; and range, 57).
Microscopy and LC quantification
Histologically all KS lesions demonstrated a prominent solid spindled and vascular growth pattern. The LC quantification results are presented in [Table 1]. The number of LCs per unit length of oral basement membrane was greatest within the covering epithelium of PAs (Control 1), with a mean of 106 cells (standard deviation (SD):50.88) [Figure 3]a, whilst the lowest cell count was within epithelium of KS + C where the mean cell count was 21 (SD: 26.32) [Figure 3]b. When LC counts were statistically compared, the difference between PAs (Control 1) and KS + C counts was highly significant (P = 0.0001) [Figure 1]a and [Figure 1]b as was the difference between PAs (Control 1) and KS − C counts (P = 0.0014) [Figure 1]a and [Figure 1]c. The LC cell counts for KS + C were also significantly different to those for KS − C (P = 0.0035).
|Table 1: Statistical comparison of Langerhans cell counts in pleomorphic adenoma, oral candidiasis and in Kaposi sarcoma with (KS+C) and without (KS-C) oral candidiasis in HIV/AIDS patients (unpaired student's t-test)|
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|Figure 3: Langerhans cell expression in palatal mucosa overlying (a) pleomorphic adenoma (PA), (b) Kaposi sarcoma with Candida(KS–C) and (c) Kaposi sarcoma without Candida (KS–C) and (d) in oral candidiasis (OC) (CD1a, DakoCytomation, Glostrup, Denmark; original magnification × 400)|
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The LC count within epithelium of OC cases (Control 2) and that of KS − C were very similar showing a moderate decrease, with a mean cell count of 45 (SD: 33.94) and 47 (SD: 51.80), respectively [Figure 3]c and [Figure 3]d. The difference between PAs (Control 1) and OC (Control 2) (P = 0.0001) was statistically significant as was the difference between OC (Control 2) KS + C counts (P = 0.0247) [Figure 1]a, [Figure 1]b, and [Figure 1]d. However, there was no statistical significance between LC counts of OC (Control 2) and KS − C (P = 0.8929).
Histologically, all KS + C and OC (Control 2) specimens showed Candida pseudohyphae characteristically penetrating the superficial keratinous epithelial layers perpendicularly to the surface, although the number of organisms varied from a few isolated hyphae to matted sheets of both hyphae and yeasts [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d. The LC count was greater in OC cases that demonstrated more intense Candida colonization.
| > Discussion|| |
This study has shown a significant depletion of LCs in palatine epithelium of oral KS coinfected with Candida (KS + C) in HIV/AIDS positive patients. When oral LCs encounter the HIV in the mouth, they capture and internalize the virus and subsequently transfer HIV to, and infect CD4 + T-cells. The number of oral LCs is considerably lower in HIV-seropositive than in HIV-seronegative subjects,,, probably because of the direct cytopathic effect of HIV on LCs, the lytic activity of cytotoxic CD8 + T-cells against LCs harboring HIV antigens  or the migration of LCs to draining lymphnodes. In turn, reduced numbers of oral LCs in HIV-seropositive subjects may predispose to local mucosal infections including OC., Some reports, however, show no significant differences between number of oral LCs in HIV-seropositive subjects with/without oral diseases  and between different HIV-seropositive subjects with various oral mucosal opportunistic infection.
In this study, the number of LCs were substantially lower in HIV-seropositive persons with palatal KS superimposed with Candida infection (KS + C), than in HIV-seropositive subjects with palatal KS but without superimposed Candida infection (KS − C). It is thus reasonable to assume that in our cases, Candida microorganisms are the cause of the decrease in numbers of LCs in affected mucosa rather than being secondary to reductions in LC numbers. This is substantiated by decreased LC counts seen in OC in otherwise healthy patients compared to those without Candida infection (PAs), increased LC counts in OC compared to HIV-seropositive KS + C cases, and the very similar LC count in OC compared to HIV seropositive KS − C. These findings suggest that reduction in LC count is most probably due to HIV infection. Romagnoli et al., reported similar results in HIV-seropositive subjects where oral tissues affected by candidiasis showed reduced number of LCs, than oral tissues without candidiasis; this reduction being more significant in oral pseudomembranous than erythematous candidiasis. This difference is attributed to a clinical manifestation of a reaction to Candida antigens as a result of defense mechanism activation.
Intraoral C. albicans is found in about 40% of healthy subjects and in up to 90% of HIV-seropositive subjects. In both these groups, the fungus colonizes the superficial layers of the epithelium without invasion of submucosa. Changes in local microenvironment such as suppressed commensal bacterial population, tissue breakdown, accumulation of inflammatory products, and lower pH, as well as local or systemic immune suppression may result in fungal overgrowth and clinical infection. HIV-seropositive subjects are particularly affected by pseudomembranous and erythematous OC and have a significantly higher carrier rate and harbor a greater variety of Candida strains.,
HIV-seropositive patients have dysregulated cytokine profiles, significantly decreased salivary flow rate, protective salivary functional activity, and lower numbers of CD4 + T-cells than HIV-seronegative subjects. All these factors may promote development of OC.,, HIV also has the capacity to enhance C. albicans virulence and to drive the evolution of phenotypically and genotypically altered strains of the fungus. Together these factors explain why OC is common in HIV-seropositive persons, and why the frequency and severity of OC increases in parallel with HIV-induced immunosuppression.
Candida exists in both commensal and pathogenic forms. The differences between these states have not been fully defined. Pathological infection with Candida is characterized by clinical lesions and immunoinflammatory reactions which are lacking in the carrier state. Many factors contribute to a change in status of Candida organisms from commensals to pathogens, including perturbed host immune defense mechanisms and change in fungal virulence factors.
OC is most common in HIV-seropositive persons when CD4 + T-cell numbers drop below 200 cells/μL and viral loads are greater than 20,000 copies/mL., The diagnosis is a clinical one and is easily confirmed with cytological smears. Since up to 60% of healthy persons are asymptomatic oral carriers of Candida, cultures are of little diagnostic value. Incisional biopsies are not indicated. The Candida carrier rate is significantly higher in HIV-seropositive patients as is the variety of strains.C. albicans is most frequently isolated species, but other species such as C. krusei and C. dubliniensis are seen with increasing frequency. Following the advent of HAART the incidence of OC has fallen dramatically.
Ortega et al., showed a reduction in OC with nonnucleoside reverse-transcriptase inhibitor HAART treatment regimen; however, in their study there were no reported cases with KS in the antiretroviral treatment (ARVT) group. If ARVT decreases the presence of OC and our study has demonstrated a significant increase in LCs in KS − C cases, then we may assume that LCs may gradually increase in number in cases following ARVT exposure. However, further investigations are required in this regard.
Occasional experimental reports have shown differences in LC number in gingivitis and periodontitis compared to clinically healthy gingiva. Segundo et al., found a quantitative increase in LCs in chronic periodontitis and no difference in LCs in gingivitis in HIV positive compared to HIV negative patients. These results differed from that of Myint et al., who found LC reduction in HIV/AIDS persons. The HIV-positive individuals in the former study were on HAART, with a low viral load, and thus showed less direct aggression by LC. These authors  suggested that the greater LC count in chronic periodontitis observed in HIV-positive individuals may possibly be associated with specific pathogens. Furthermore, they found no statistically significant correlation in LC count, CD4 T-cells, CD8 T-cells, or viral load, which they attributed to the fact that all HIV positive patients were on HAART with low viral loads and standard accepted levels of CD4 and CD8 T-cells. The use of HAART aids in attaining low viral loads, with possible prevention of LC destruction in the gingiva of these patients with periodontitis. These studies are preliminary and further studies investigating LC function in HIV/AIDS are warranted. A major drawback is the failure of HAART to remove reservoirs of HIV and restore CD4 + T-cell function. This has thus necessitated the search for alternate immunotherapies. Thus, the use of dendritic cells has become popular in proposed methods of HIV vaccine development.
Neutrophils are anti-candidal effector cells, and Th17 and/or Th1 cells mediate the killing of C.albicans by neutrophils. In one study, neutrophils were missing in the inflammatory infiltrate of HIV-seropositive subjects with either erythematous or pseudomembranous candidiasis, most probably owing to defective recruitment of these cells by T-cells in the context of HIV-induced T-cell depletion.
From our experience we noted that biopsies taken from oral KS are frequently coinfected with Candida and that this tissue, which is readily available, might be used in studying OC-HIV-epithelial interactions in situ, in HIV/AIDS patients. It is surprising that only 50% of biopsy specimens showed coinfection with Candida in the epithelial surface of lesional tissue. Since these patients already have an AIDS-defining disease, we would have expected this percentage to have been much higher.
The number of LCs in normal oral mucosa varies according to site. The highest LC numbers are found in the nonkeratinized mucosa of the soft palate and ventral surface of tongue, lip, and vestibule; while lower counts are found in keratinized mucosa of the hard palate, gingiva, and floor of mouth. The only site where they are not found is in junctional epithelium., The absolute numbers at any one time may vary depending on the nature and intensity of the antigenic challenge. Abnormalities in number and function of LCs have been implicated in the pathogenesis of several diseases of the oral mucosa, amongst which are lichen planus, oral mucosal infections, HIV-associated infections, LC histiocytosis, and periodontal disease.
Only a few studies explore the possible relationship between LC and OC and these differ in their conclusions., One reported a decrease in number and a change in distribution of LCs in chronic hyperplastic candidiasis, but this difference was not statistically significant, possibly due to small sample size. Another reported that LCs were absent in median rhomboid glossitis. In seropositive patients, LCs were also reported to be absent in biopsy specimens of hairy leukoplakia. Inflamed gingival epithelium can display a variety of changes in LC numbers—they may increase, decrease, or show no quantitative change. Discrepancies in the various studies may be due to differences in stage of the disease. In an experimental study on chronic periodontitis an increase in numbers of LC was observed until day 7 followed by a plateau and then a decrease by day 21. Our study showed a statistically significant decrease in LC counts in OC in apparently healthy individuals compared to oral mucosa with no Candida infection. This decreased LC count, however was still statistically significantly higher than that seen in oral mucosa of HIV seropositive individuals infected with Candida.
LCs are the initial target cell for HIV, and are responsible for transfer of virus to CD4 + T-cells, thus spreading the infection. Furthermore, LCs induce a virus specific immune response in draining lymph nodes. They take up candidal antigens and induce a similar cellular response in patients with oropharyngeal candidiasis. They also play a role in the innate response where they have been shown to influence migration of polymorphonuclear cells. Multiple defects in LCs contribute to progressive loss of cell mediated immune responses. A decrease in LC numbers, decreased expression of major histocompatibility complex (MHC) II, blunt dendrites, limited development of organelles, and lack of Birbeck granules are amongst the defects that have been implicated. Progressive reduction of CD8 + T-cells, a striking reduction in CD4 + T-cells, a switch to Th2 cytokine profile, and phagocyte defects could also predispose to oropharyngeal candidiasis in patients with HIV infection.
In conclusion, in HIV-seropositive patients the number of LCs is significantly reduced in palatal tissues affected by Candida infection when compared to oral mucosal tissues with and without fungal infection in HIV-seronegative patients. It appears that HIV infection induces cytopathic changes in LCs, contributing to their depletion regardless of the presence of oral infections. Since we did not have patient information regarding whether patients were on HAART, displayed OC clinically and patient CD4 + T-cell counts, further studies investigating the role of these factors on numbers of oral LCs found in KS lesions are warranted.
| > References|| |
Barrett AW, Cruchley AT, Williams DM. Oral mucosal Langerhans' cells. Crit Rev Oral Biol Med 1996;7:36-58.
Cutler CW, Jotwani R. Dendritic cells at the oral mucosal interface. J Dent Res 2006;85:678-89.
Séguier S, Godeau G, Brousse N. Immunohistological and morphometric analysis of intra-epithelial lymphocytes and Langerhans cells in healthy and diseased human gingival tissues. Arch Oral Biol 2000;45:441-52.
Upadhyay J, Upadhyay RB, Agrawal P, Jaitley S, Shekhar R. Langerhans cells and their role in oral mucosal diseases. N Am J Med Sci 2013;5:505-14.
Mesman AW, Geijtenbeek TB. Pattern recognition receptors in HIV transmission. Front Immunol 2012;3:59.
Gondak RO, Alves DB, Silva LF, Mauad T, Vargas PA. Depletion of Langerhans cells in the tongue from patients with advanced-stage acquired immune deficiency syndrome: Relation to opportunistic infections. Histopathology 2012;60:497-503.
Spörri B, von Overbeck J, Brand CU, Schmidli J, Sanchez ML, Grunow R, et al
. Reduced number of Langerhans cells in oral mucosal washings from HIV-1 seropositives. J Oral Pathol Med 1994;23:399-402.
Chou LL, Epstein J, Cassol SA, West DM, He W, Firth JD. Oral mucosal Langerhans' cells as target, effector and vector in HIV infection. J Oral Pathol Med 2000;29:394-402.
de Repentigny L, Lewandowski D, Jolicoeur P. Immunopathogenesis of oropharyngeal candidiasis in human immunodeficiency virus infection. Clin Microbiol Rev 2004;17:729-59.
Romagnoli P, Pimpinelli N, Mori M, Reichart PA, Eversole LR, Ficarra G. Immunocompetent cells in oral candidiasis of HIV-infected patients: An immunohistochemical and electron microscopical study. Oral Dis 1997;3:99-105.
Dongari-Bagtzoglou A, Fidel PL Jr. The host cytokine responses and protective immunity in oropharyngeal candidiasis. J Dent Res 2005;84:966-77.
Reichart PA. Oral manifestations in HIV infection: Fungal and bacterial infections, Kaposi's sarcoma. Med Microbiol Immunol 2003;192:165-9.
Lü FX, Jacobson RS. Oral mucosal immunity and HIV/SIV infection. J Dent Res 2007;86:216-26.
Challacombe SJ, Naglik JR. The effects of HIV infection on oral mucosal immunity. Adv Dent Res 2006;19:29-35.
Fidel PL Jr. Candida-host interactions in HIV disease: Relationships in oropharyngeal candidiasis. Adv Dent Res 2006;19:80-4.
Nicolatou-Galitis O, Velegraki A, Paikos S, Economopoulou P, Stefaniotis T, Papanikolaou IS, et al
. Effect of PI-HAART on the prevalence of oral lesions in HIV-1 infected patients. A Greek Study. Oral Dis 2004;10:145-50.
Ortega KL, Vale DA, Magalhães MH. Impact of PI and NNRTI HAART on HAART-based therapy on oral lesions of Brazilian HIV-infected patients. J Oral Pathol Med 2009;38:489-94.
Segundo TK, Souto GR, Mesquita RA, Costa FO. Langerhans cells in periodontal disease of HIV- and HIV+patients undergoing highly active antiretroviral therapy. Braz Oral Res 2011;25:255-60.
Myint M, Yuan ZN, Schenck K. Reduced numbers of Langerhans cells and increased HLA-DR expression in keratinocytes in the oral gingival epithelium of HIV-infected patients with periodontitis. J Clin Periodontol 2000;27:513-9.
Van Gulck E, Van Tendeloo VF, Berneman ZN, Vanham G. Role of dendritic cells in HIV-immunotherapy. Curr HIV Res 2010;8:310-22.
Daniels TE, Greenspan D, Greenspan JS, Lennette E, Schiødt M, Petersen V, et al
. Absence of Langerhans cells in oral hairy leukoplakia, an AIDS-associated lesion. J Invest Dermatol 1987;89:178-82.
Walsh LJ, Cleveland DB, Cumming CG. Quantitative evaluation of Langerhans cells in median rhomboid glossitis. J Oral Pathol Med 1992;21:28-32.
Pope M. Mucosal dendritic cells and immunodeficiency viruses. J Infect Dis 1999;179:S427-30.
Scimone ML, Lutzky VP, Zitterman SI, Maffia P, Jancic C, Buzzola F, et al
. Migration of polymorphonuclear leucocytes is influenced by dendritic cells. Immunology 2005;114:375-85.
[Figure 1], [Figure 2], [Figure 3]