14th International AIDS Conference Barcelona, Spain - July 7-12, 2002

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. WeOrA1348)

Muthukumar A, Wozniakowski A, Matthews C, Douek DC, Johnson RP, McClure HM, Koup RA, Sodora DL
UT Southwestern Medical Center at Dallas, Dallas, Texas -75390-9113, United States

BACKGROUND: CD4+ T cell depletion is a hallmark of HIV/SIV infection. The thymus is responsible for de novo production of T lymphocytes, and therefore is important for T cell renewal. HIV infection in humans, as well as SIV infection of macaques, results in thymic atrophy, reflecting a possible decrease in T cell production. Methods and

RESULTS: We assessed the role of the thymus following a pathogenic SIV infection by comparing thymectomized macaques (n=3) to controls with an intact thymus (n=3). As a quantitative measure of thymic output, levels of recent thymic emigrants were determined by measuring T cell receptor excision circles (TREC). Quantification of peripheral blood TREC levels showed two distinct phases of SIV infection. Phase 1 was marked by a slight increase or sustained level of TREC, whereas phase 2 was associated with decreasing TREC levels. For thymectomized macaques phase 1 lasted approximately 12-16 weeks compared to 16-30 weeks for the control group. During phase 2, TREC levels declined at similar rates for both groups. Assessment of naïve/memory phenotype, CD4/CD8 levels, Ki67 staining and other activation markers suggest that declining TREC levels results from the contribution of both increased T cell proliferation (expression of Ki67) and decreased thymic output. Examination of the thymic tissue obtained at necropsy demonstrated characteristic pathology including an increase in the percentage of mature CD8+ T cells and increased levels of apoptotic/TUNEL+ cells.

CONCLUSIONS: We have documented a reduction in the levels of recent thymic emigrants and distinct thymic pathology following SIV infection, however the impact of thymectomy on disease progression was not dramatic. TREC analysis permitted the infection to be divided into two distinct phases. Prolonged phase 1 (sustained TREC levels) in macaques with a thymus indicated that the thymus is important for maintaining the naïve T cell pool at early times post-infection.

020707
WeOrA1348

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