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p59^fyn (Fyn) Promotes the Survival of Anergic CD4^-CD8^- TCR⁺ Cells but Negatively Regulates Their Proliferative Response to Antigen Stimulation¹

Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada

T cell anergy is characterized by alterations in TCR signaling that may play a role in controlling the unresponsiveness of the anergic cell. We have addressed questions regarding the importance of the Src kinase p59^fyn (Fyn) in this process by using Fyn null mice. We demonstrate that a mature population of CD4^-CD8^- TCR⁺ anergic T cells lacking Fyn have a substantial recovery of their proliferation defect in response to Ag stimulation. This recovery cannot be explained by ameliorated production of IL-2, and the improved proliferation correlates with an enhanced ability of the Fyn^-/- anergic T cells to up-regulate the high affinity IL-2 receptor. We also observe that anergic CD4^-CD8^- TCR⁺ T cells have a heightened survival ability that is partially dependent on the elevated levels of Fyn and IL-2 receptor -chain expressed by these cells. The enhanced survival correlates with an increased capacity of the anergic cells to respond 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.

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