Local Immune Reactivity in Oral Warts and Oral Hairy Leukoplakia of HIV-Infected Persons

E Lilly, K Shetty, K Mcnulty, JE Leigh, JE Cameron, ME Hagensee, PL Fidel*

Louisiana State University Health Sciences Center and Center of Excellence in Oral and Craniofacial Biology, New Orleans, LA 70112 USA

P Fidel: pfidel@lsuhsc.edu

Background: Oral hairy leukoplakia (OHL) caused by Epstein Barr virus and oral warts caused by human papillomavirus (HPV) are common infections in HIV-infected persons. Although each pathological condition occurs most often under reduced blood CD4 cell numbers, the lack of concurrent pathologies suggests that each results from unique local immune dysfunction(s).

Objective: To evaluate local immune reactivity in oral warts and OHL through salivary cytokines and tissue-associated T cells and cytokine mRNA.

Methods: A cohort of HIV+ persons (n=48) with and without oral warts and OHL were evaluated. Salivary Th and proinflammatory cytokines were quantified in unstimulated saliva by ELISA. CD3, CD4, and CD8 T cells were identified by immunohistochemical staining of frozen tissue biopsies. Tissue-associated cytokine mRNA was evaluated by real-time PCR.

Results: Few differences were detected in any parameter. Compared to matched controls (HIV+ persons without lesions but positive for oral HPV or EBV DNA), those with OHL had increased IL-1, IL-2 and IL-10 in saliva, while those with oral warts had increased IL-1, IL-2 and decreased IL-6. CD8 T cells predominated in the tissue but in low numbers. No differences were detected between warts and lesion negative sites, while CD8 T cells were greater in lesion negative sites compared to OHL. Tissue-associated cytokine mRNA between lesion positive and lesion negative persons showed decreased IL-2 and increased TNF in those with warts, and decreased IL-1 and increased IL-6 and IL-15 in those with OHL

Conclusion: There is no pattern of changes in local immunity to explain the susceptibility to oral warts and OHL, and overall little evidence for local immune reactivity in either lesion. It is anticipated that while immunosuppression plays an indirect role in susceptibility to infection, virologic factors are most critical to prevalence.