108 CD127 EXPRESSION ON THYMIC SUBSETS IS DIFFERENTIALLY DOWNREGULATED FOLLOWING IN VITRO HIV INFECTION C Young, J Angel Background: Thymic function is altered in HIV infection leading to a dysregulation of the thymic epithelial network, reduced thymic output and therefore an impaired naïve T-cell pool. The IL-7/IL-7R (CD127) signaling pathway is critical for the maturation and differentiation of thymocytes. Since CD127 expression is decreased on circulating CD8 cells in HIV infection we hypothesize that impaired thymic function in HIV infection is due to a decrease in CD127 expression on developing thymocytes.
Ottawa Health Research Institute, Ottawa, Ontario
Methods: Thymii were obtained from children undergoing elective cardiac surgery and thymocytes were isolated using established methods. Thymocytes were infected at an MOI of 0.001 with an X4 viral strain (HIVIIIB), a dual tropic viral strain (HIVCS204) or a replication incompetent viral strain (HIV8E5) prior to co-culture with allogeneic thymic epithelial cells. Expression of CD127 was determined by flow cytometry on the thymocyte subset representing the various developmental stages of T-cell maturation: triple negative CD3-CD4-CD8-(TN), immature single positive CD3-CD4+CD8-(ISP4), double positives CD3-CD4+CD8+(CD3-DP), CD3+CD4+CD8+(CD3+DP) and single positive cells CD3+CD4+CD8-(SP4) and CD3+CD4-CD8+(SP8).
Results: Within the thymus the most prominent sub-population is the DP CD3-CD4+CD8+ subset. All thymocyte subsets express CD127, however to varying degrees, where SP8 express CD127 to the greatest degree. Thymocyte infection with HIVIIIB resulted in decreased expression of CD127 on cells within the SP4 and SP8 subsets but not on cells of the CD3+DP subset. In contrast, in thymocytes infected with HIV8E5 no downregulation of CD127 expression was seen.
Conclusion: In vitro HIV infection alters CD127 expression on thymocytes, suggesting that HIV may play a role in impaired thymic function by altering the IL-7 responsiveness of thymocytes. It appears that the various thymocyte subsets are differentially affected by HIV infection. These results may provide some insight into how HIV infection results in impaired thymic function.