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Session 47 Poster Presentations Immunology: NK Cell, Cytokine, and Innate Immune Responses Session Day and Time: Thursday 1:30 - 3:30 pm Room: Hall D

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No Changes in Immune Activation Phenotypes, Response to Antigen, or CD8⁺ T-cell Mediated HIV Suppression in Transplant Recipients Receiving Immunosuppression
M. Roland*¹, D. Stablein², B. Bredt¹, B. Munoz-Marino¹, L. Carlson¹, J. McCune¹, J. Levy¹, R. Rogers¹, P. Stock^1
1Univ of California at San Francisco and ²EMMES Corp, Rockville, MD

Background: HIV infection is associated with loss of "naïve" T-cells, activation of "memory" T-cells, loss of CD4⁺ T-cell proliferative responses to recall antigens and T-cell mitogens, and loss of normal responses to antigen by activated CD8⁺ T-cells. Cyclosporine (CsA) may reduce immune activation-associated HIV pathogenesis. Previous studies show no change in immune activation markers with low dose CsA; substantial CD4⁺ T-cell increases were seen in primary HIV infection treated with CsA at levels typically used in transplant, plus a protease inhibitor. We evaluated changes in markers of immune activation, naive and memory phenotypes, T-cell responses to antigen, and CD8⁺ T-cell non-cytotoxic anti-HIV response (CNAR) in HIV⁺ transplant recipients receiving CsA.
Methods: Naïve (CD45RA⁺CD62L⁺), memory/effector (CD45RA^-CD62L⁺/CD45RA ±CD62L^-) CD4⁺ and CD8⁺ T-cells and activated (CD38⁺ and/or HLA-DR⁺) CD4⁺ and CD8⁺ T-cells were analyzed by flow cytometry. T-cell response directed against SEB and CMV were evaluated using intracellular cytokine flow cytometry assays. CNAR was measured by mixing subject CD8⁺ T-cells with normal CD4⁺ T-cells infected with a chemokine insensitive HIV-1 strain (SF33). HIV replication was measured by reverse transcriptase activity (RT). Percentage of suppression was calculated compared to average RT in CD4⁺ T-cells grown alone.
Results: Nine (9) subjects were studied pre-transplant and at = 2 of the following time points: weeks 2, 4, 12, 28, and 52 post-transplant. No changes were observed in the percentages of CD4⁺CD3⁺ (p = 0.9) or CD8⁺CD3⁺ T-cells (p = 0.12), of naïve (CD45RA⁺CD62L⁺) CD4⁺ (p = 0.4), or CD8⁺ T-cells (p = 0.3), of memory/effector (CD45RA^-CD62L⁺/CD45RA⁺CD62L^-) CD4⁺ (p = 0.53), or CD8⁺ T-cells (p = 0.17) or in the expression of the activation markers CD38 or HLA-DR on CD4⁺ or CD8⁺ T-cells (all p > 0.4). At wk 4, CD38⁺/DR⁺ CD4⁺ T-cells decreased (p < 0.001), but this change did not persist. No changes were observed in the ability of CD4⁺ T-cells to produce TNFalpha or IFNgamma in response to stimulation by SEB or CMV antigens (all p > 0.5). Five (5) subjects who completed wk 52 were evaluated for CNAR. There were no consistent patterns of CNAR activity either pre-transplant or post-transplant compared to pre-transplant.
Conclusions: Except for a transient decrease in activated CD4⁺ T-cells, no statistically significant changes were observed in markers of immune activation or function measured over 1 yr in CsA-treated HIV⁺ transplant recipients.

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