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Abstract
IMPACT OF IL-7 ON ADULT HUMAN THYMIC SUBSETS
JAMIESON B, ZACK J, SCRIPTURE-ADAMS D
Our previous data show that the adult thymus generates new thymocytes similar to fetal thymocytes in their subset distributions, response to co-stimulatory signals, and diversity of TCR-Vb repertoires, suggesting that newly formed T-cells in adults may functionally respond to a broad array of antigens. In collaborations we also documented the presence of recent thymic emigrants in the periphery of HIV-infected adults on HAART. These data suggest that the adult thymus retains the potential to contribute to T-cell reconstitution in HIV-infected individuals. Reconstitution is slower in adults than children due to the decreased cellular output of the adult thymus. We are investigating potential therapeutics to increase adult thymic function to augment T-cell reconstitution. We established an in vitro culture system (ATOC) that supports viable endogenous thymocyte development in adult thymic tissue. Since IL-7 is required for pro-thymocyte development and for the promotion of immature thymocyte survival, we used ATOC to assess the effect of IL-7 on adult thymopoeisis. IL-7 increased the percentage of CD8+ and CD4+/CD8+ (DP) thymocytes recovered from the ATOC, and increased the percentage of CD4+CD3-CD8- immature thymic precursors recovered early in the culture period. Interestingly, although similar changes were seen in fetal tissues and cells with respect to mature, and immature subsets, the fetal DP population did not increase with IL-7, but actually decreased in percentage. Subset specific increases in RNA production and progression of thymocytes into S, G2 and M phases were detected in both adult and fetal thymuses when IL-7 was added to cultures. Our data provides further evidence of the proper functioning of the adult thymus, and demonstrates the ability of IL-7 to promote thymocyte, maturation and proliferation in adult thymic organ cultures. As such, IL- 7 remains an attractive therapeutic candidate to increase T-cell reconstitution in the context of HAART.
The 1st. IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
80
Suggested Citation
"JAMIESONB, et al.
IMPACT OF IL-7 ON ADULT HUMAN THYMIC SUBSETS.
Oral Presentation:
The 1st. IAS Conference on HIV Pathogenesis and Treatment
:
Abstract no.
80"
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