Abstract 376 - IL-7 Prevents Apoptosis of Thymic Progenitor Cells Induced by HIV and Contributes to T Cell Reconstitution in the Thymus.

376 IL-7 Prevents Apoptosis of Thymic Progenitor Cells Induced by HIV and Contributes to T Cell Reconstitution in the Thymus.

Y. Okamoto*, D. C. Douek, and R. A. Koup.
Univ. of Texas Southwestern Med. Ctr., Dallas.

Background:Immune reconstitution is a critical aspect of the treatment of HIV disease. Here we examined the effects of IL-7 on survival and TREC generation of thymic progenitor cells exposed to HIV in a single-cell suspension culture system.

Methods:Fetal thymocytes were sorted into immature cells which have not yet generated TREC, comprising the CD3^-CD4^-CD8^-and CD3^-CD4^low/+CD8^-subsets, and then cultured with or without IL-7. TREC levels of these cells before culture were lower than 100 copies /10,000 cells.

Results:TREC generation was detected from day 4 and showed a significantly higher level (p < 0.03) with IL-7 (4,078 + 1,056 and 2,298 + 1,043 per 10,000 cells for IL-7 and control, respectively). The percentage of differentiated CD4⁺CD8⁺cells in the culture with IL-7 was significantly lower compared with the control culture. This suggests that IL-7 maintains survival of immature cells and stimulates the initiation of TREC generation by controlling the differentiation to following stages. High doses of HIV_BRU, but not HIV_JR-CSF, induced apoptosis of progenitor cells, and more than 90% of cells were dead by day 4. Strikingly, IL-7 prevented this apoptosis of the majority of cells even with continual exposure of HIV. Moreover, IL-7 levels in the supernatant of thymic organ culture (TOC) were significantly increased with infection of HIV_BRUbut not HIV_{JR- CSF}. We are currently examining the HIV copy number in each cell as measured by Taqman PCR, as well as TREC generation in the HIV-infected cultures.

Conclusions:These findings demonstrate that exogenous IL-7 supports the survival of thymic progenitor cells exposed to HIV infection by protecting them from apoptosis. The increase of IL-7 production in TOC with HIV_BRUinfection suggests that the survival of progenitor cells in the thymus is enabled by the IL-7 produced in response to HIV infection.