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Increasing Thymic Output with Exogenous IL-7 Y. OKAMOTO*, D. C. DOUEK, R. D. MCFARLAND, and R. A. KOUP. Univ. of Texas Southwestern Med. Ctr., Dallas Immune reconstitution is a critical aspect of the treatment of HIV disease. Recently, using T cell receptor rearrangement excision circles (TRECs) to measure thymic output, we demonstrated that the adult thymus maintains thymopoiesis and can contribute to T cell reconstitution. HIV infection disrupts thymic architecture and impairs thymopoiesis. Here we examined the effects of exogenous IL-7 on thymic output. In the thymus organ culture (TOC) system, IL-7 increased the number of mature and immature thymocytes in a dose-dependent manner in fetal thymus. It also increased the frequency of TRECs within early thymocytes, indicating increased TCR rearrangement. In a 3 year old thymus, IL-7 significantly increased TREC levels after the addition of CD34+ progenitor cells. The effects of IL-7 were also observed in NOD-scid-hu mice following administration of IL-7 by intraperitoneal injection for 10 days. The weight of the grafts in the IL-7 inoculated group (n=11) was greater than controls (n=9), and TREC level in grafts and PBMC were significantly higher than in controls. In TOC infected with CXCR4- or CCR5-tropic HIV-1, IL-7 increased TREC levels, although there was concomittant enhancement of CXCR4 and CCR5 expression and HIV replication. These results indicate that IL-7 can stimulate thymopoiesis in fetal and infant thymuses and suggest the possibility of its use with HAART to promote T cell reconstitution. Key Words: HAART, IL-7, Thymopoiesis |
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© 7th
Conference on Retroviruses and Opportunistic Infections, |