OBJECTIVE: Dasatinib (BMS-354825) is a small molecule Src/Abl tyrosine kinase 
inhibitor approved for the treatment of chronic myeloid leukemia and 
Philadelphia chromosome-positive acute lymphoblastic leukemia. Members of the 
Src family of kinases are involved in the induction of innate and adaptive 
immunity. The purpose of this study was to evaluate the inhibitory action of 
dasatinib on antigen-specific CD8(+) and CD4(+) T-cell function, as well as 
natural killer (NK) cell cytotoxicity.
MATERIALS AND METHODS: To assess dasatinib-mediated inhibition of 
antigen-specific T-cell proliferation, transgenic CD4(+) and CD8(+) T cells 
specific for ovalbumin were utilized. Endogenous CD4(+) and CD8(+) T-cell 
responses were determined following immunization of dasatinib-treated or control 
mice with a nonreplicating recombinant virus. Clearance of the RMA-S cells, a 
major histocompatibility complex (MHC) class I-deficient thymoma sensitive to 
NK-cell lysis, was analyzed in mice undergoing dasatinib treatment.
RESULTS: Dasatinib inhibited antigen-specific proliferation of murine CD4(+) and 
CD8(+) transgenic T cells in vitro and in vivo. Endogenous antigen-specific 
helper T-cell recall responses and induction of T-cell-mediated cytotoxicity 
following immunization with a nonreplicating recombinant virus were also 
inhibited. So to was the ability of NK cells to eliminate MHC class I-deficient 
cells in vivo.
CONCLUSIONS: These findings suggest that dasatinib has the potential to modulate 
the host immune response at clinical doses and highlights scope for off target 
applications, e.g., therapeutic immunosuppression in the context of autoimmune 
pathogenesis and allogeneic tissue transplantation.