Background: We found that upregulation of Hck mRNA expression, an Src family tyrosine kinase, in surveillance graft biopsies of kidney transplant patients associates with an increased risk of developing acute rejection subsequently (JASN 2016). Whether Hck regulates T cell responses is unknown.

Methods: We tested Hck expression in various murine tissues by quantifying mRNA expression. In functional experiments, we activated CFSE-labeled PBMCs from healthy humans with anti-CD3 mAb or cultured naïve CD4+ T cells in Treg polarizing conditions (anti-CD3/CD28 mAb, IL-2, TGF-b) in the presence or absence of a nonspecific tyrosine kinase inhibitor dastatinib or a selective Hck inhibitor, BT294. At 5 days, we measured CFSE dilution, IFN-γ production, and percentages of FOXP3+ cells, respectively.

Results: Hck is expressed in T cells (Fig. 1A). Both dasatinib and BT294 significantly decreased CD4 and CD8 T-cell proliferation in a dose dependent manner, while only dasatinib, but not BT294 decreased IFN-γ production (Fig. 1B). BT294 decreased percentage of FOXP3+ induced Treg (Fig. 1C).

Conclusions: Hck is expressed in T cells and is implicated in T cell expansion and Treg induction, but not in IFN-g production, providing a potentially novel potential target for selective immunosuppressive therapies.

CITATION INFORMATION: Farouk S., Wei C., Das B., Cravedi P., Murphy B. Hematopoietic Cell Kinase (Hck) Regulates Effector and Regulatory T Cell (Treg) Function Am J Transplant. 2017;17 (suppl 3).

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