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Down‐regulation of IL‐7R on memory CD4+ T cells correlates with expression of cytotoxic granule proteins

Survival of activated T cells into long‐lasting memory cells has been shown to be dependent on expression of IL‐7 receptor (IL‐7R) at the peak of the immune response. The memory phenotype of cytotoxic CD4+ T cells is poorly defined compared to CD8+ T cells. The objective of these studies was to correlate IL‐7R expression on activated CD4+ T cells with expression of cytotoxic granule proteins: granulysin, perforin, and granzyme B. Our results demonstrate that TCR activated CD4+ T cells within peripheral blood down regulate IL‐7R as the cells divide and this down‐regulation of IL‐7R and CCR7 positively correlates with enhanced expression of granzyme B, granulysin, and perforin. After TCR activation of sorted CD4+ T cell memory subsets, the highest level of granulysin and perforin mRNA was observed in CD45RO+IL‐7R‐ CD4+ T cells. In contrast, granzyme B mRNA levels were most significantly increased in the CD45RO+IL‐7R+ subset and correlated with down‐regulation of IL‐7R levels. Our data suggests that although the IL‐7R+ memory CD4+ T cells lack immediate expression of cytotoxic proteins, upon secondary stimulation, these memory cells down‐regulate IL‐7R and give rise to IL‐7R−CD4+ T cells with cytotoxic potential. This research is supported by the Dept. of Microbiology and Immunology, UTMB.