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Session 25 Oral Abstract Session Immunology Session Time: Wednesday, 10 am - 12:30 pm Room 6C

10:00   101. Impact of Thymectomy on the Peripheral T-Cell Pool in Rhesus Macaques before and after Infection with SIV S. T. Arron1, A. Gettie2, J. Blanchard1, 2, D. Ho1, and L. Zhang*1 1Aaron Diamond AIDS Res. Ctr., Rockefeller Univ., New York, NY and 2Tulane Regional Primate Res. Ctr., Covington, LA Background: The goal of this study is to define the role of the thymus in peripheral T-cell homeostasis and to assess the significance of thymic output in SIV infection by surgical removal of the thymus in juvenile rhesus macaques. Methods: 9 juvenile rhesus macaques were thymectomized and 8 underwent sham surgery. Blood was drawn periodically in the 9 months following surgery and for the subsequent 6 months following SIV infection, and assayed for plasma viral loads, lymphocyte subsets, and the concentration of T-cell receptor excisional circles (TREC). Results: In the 9 months post-surgery, there were no statistical differences in the decay rates of CD3+, CD4+, CD8+, CD3+CD45RA+, CD4+CD45RA+, CD8+CD45RA+, and Ki67+ proliferating T cells in blood between thymectomy and sham groups. We found that TREC decay rates in peripheral CD4+ (-0.0046) and CD8+ (-0.0065) T cells of thymectomized macaques, however, were significantly higher than those in sham controls (p<0.05). Based on the decay slope of TREC post thymectomy, we have calculated an absolute thymic production rate of ~5.5 x 106 to 1.1 x 107 TREC-bearing cells per day, which is quantitatively insignificant among the total T-cell pool of ~1011 in rhesus monkeys. After infection with SIV, no significant differences in peak or setpoint viral loads and in decay rates of the same lymphocyte subsets studied above were noted between infected thymectomized and sham groups. Infection increased the decay of TREC in peripheral T cells in both groups. However, slopes adjusted for the pre-infection difference in decay between 2 groups demonstrated no significant difference in TREC decay between the 2 groups after infection. Conclusions: Surgical thymectomy in juvenile macaques did not cause a loss of peripheral T cells or a shift in naïve and memory populations. No compensatory extra-thymic source was detected, nor was there evidence of compensatory T-cell proliferation. After SIV infection, the absence of the thymus did not result in higher viral loads, greater T-cell decay, or faster disease progression. While SIV infection has been reported to have pathogenic effects on the thymus, such involvement probably plays a minimal role in the depletion of CD4+ lymphocytes, given our current findings. Taken together, this study shows that peripheral destructive processes, rather than a loss of thymic output, are responsible for T-cell depletion in SIV infection and, by inference, HIV infection.

©2002 9th Conference on Retroviruses and Opportunistic Infections