Mice Lacking Protein Tyrosine Kinase Fyn Develop a T Helper-Type 1 Response and Resist \it{Leishmania major} Infection

ABSTRACT

Fyn is a Src family protein tyrosine kinase associated with TCR/CD3 complex. Fyn appears to play a role in the activation of T cells based on its enzymatic activation and tyrosine phosphorylation following the ligation of TCR/CD3, and it also plays a critical role in the calcium flux and interleukin-2 (IL-2) production. The protective response against murine Leishmania major infection is associated with the T helper-type 1 (Th1) responses and the ability to modulate Th1 cytokines such as IL-2 and interferon-γ, respectively. The role of Fyn tyrosine kinase in vivo was directly examined by the response to infection with L. major in C57BL/6 fyn-deficient mice. Despite the absence of Fyn, the mice remained resistant to this infection with only mild lesion development, and, they demonstrated Th1 responses as assessed by the delayed-type hypersensitivity response and cytokine milieu. The findings in the fyn-deficient mice failed to support a relationship between the anticipated functions of Fyn in vitro and the immune response to L. major infection in vivo. As a result, in leishmanial disease, Fyn probably plays a minor role in the protective immune response and is, therefore, not a key factor in such a response.