379 HIV Infection is Associated with Expanded Mucosal gamma delta T-cells, which may Explain Changes in Peripheral gamma delta T-cell Counts M. A. Poles*1,2, S. Barsoum1,2, P. Sun1, D. Ho2, L. Zhang2 1New York Univ Sch of Med, New York and 2Aaron Diamond AIDS Res Ctr, New York, NY
Background: Gamma delta T-cells, potentially important components of the innate immune response against HIV, are primarily found in the gastrointestinal mucosa.
Methods: We utilized flow cytometry to phenotype lymphocytes derived from the peripheral blood and from colonic biopsies of HIV-infected and uninfected subjects. Statistical comparisons were made between peripheral blood and mucosal mononuclear cells from individuals using a paired t-test. Statistical comparisons were made between HIV-1 infected and control subjects using a 2-sample, equal variance (homoscedastic) t-test.
Results: HIV-1 infected subjects without diagnosed colonic disease had a significantly greater percentage of T-cells expressing the gamma delta T-cell receptor in their colonic mucosa compared to healthy subjects (26.1 ±18.4 vs 13.2 ± 5.2%, p = 0.04). In infected subjects, Vdelta1 cells comprised the dominant population of gamma delta T-cells in both the mucosa (58.1 ±19.1) and peripheral blood (60.2 ±10.5), occurring at the expense of the Vdelta2 population that represents the dominant population in healthy controls. HIV infection is associated with an increase in the percentage of peripheral blood gamma delta T-cells that express either the mucosal homing receptors CCR9 or CD103, (1.2 ±1.4% vs 2.7 ±2.1%, p = 0.05). We also found that HIV-1 infection is associated with an increase in the percentage of peripheral blood gamma delta T-cells that express the activation marker HLA-DR. This population of gamma delta T-cells equaled that seen in the mucosa (p = 0.89) and was significantly increased from that found in the blood of HIV seronegative subjects (p = 0.02). We noted a significantly smaller percentage of gamma delta T-cells that expressed CD45RO in both the blood (p = 0.001) and mucosal (p = 0.07) of HIV-infected subjects.
Conclusions: Based on these findings, we conclude that HIV infection results in expansion of the mucosal gamma delta T-cell population. Given the increase in peripheral Vdelta1 gamma delta T-cells, a population normally largely restricted to the gastrointestinal mucosa, increased expression of mucosal homing receptors may indicate homing to or egress from the gastrointestinal mucosa. This is also supported by data showing similar expression of CD45RO and HLA-DR between these compartments in HIV-infected subjects.