p59(fyn) (Fyn) promotes the survival of anergic CD4(-)CD8(-) alpha beta TCR+ cells but negatively regulates their proliferative response to antigen stimulation

T cell anergy is characterized by alterations in TCR signaling that may pla y a role in controlling the unresponsiveness of the anergic cell. We have a ddressed questions regarding the importance of the Src kinase p59(fyn) (Fyn ) in this process by using Fyn null mice. We demonstrate that a mature popu lation of CD4(-)CD8(-) alpha beta TCR+ anergic T cells lacking Fyn have a s ubstantial recovery of their proliferation defect in response to Ag stimula tion. This recovery cannot be explained by ameliorated production of IL-2, and the improved proliferation correlates with an enhanced ability of the F yn(-/-) anergic T cells to up-regulate the high affinity IL-2 receptor. We also observe that anergic CD4(-)CD8(-) alpha beta TCR+ T cells have a heigh tened survival ability that is partially dependent on the elevated levels o f Fyn and IL-2 receptor beta -chain expressed by these cells. The enhanced survival correlates with an increased capacity of the anergic cells to resp ond to IL-15. We conclude that Fyn plays an important role in aspects of T cell anergy pertaining to TCR signaling and to cell survival.