Normal Development and Activation but Altered Cytokine Production of Fyn-Deficient CD4+ T Cells

• Published in: The Journal of immunology (1950) Vol. 181; no. 8; pp. 5374 - 5385
• Main Authors: Mamchak, Alusha A, Sullivan, Brandon M, Hou, Baidong, Lee, Linda M, Gilden, Julia K, Krummel, Matthew F, Locksley, Richard M, DeFranco, Anthony L
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15-10-2008
• Subjects: Animals; Antigen-Presenting Cells - immunology; Antigens - genetics; Antigens - immunology; CD28 Antigens - immunology; CD4-Positive T-Lymphocytes - immunology; Cell Differentiation - genetics; Cell Differentiation - immunology; Cell Proliferation; Histocompatibility Antigens Class II - genetics; Histocompatibility Antigens Class II - immunology; Interleukin-4 - genetics; Interleukin-4 - immunology; Killer Cells, Natural - immunology; Mice; Mice, Inbred BALB C; Mice, Knockout; Proto-Oncogene Proteins c-fyn - genetics; Proto-Oncogene Proteins c-fyn - immunology; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - immunology; Signal Transduction - genetics; Signal Transduction - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.181.8.5374

The Src family kinase Fyn is expressed in T cells and has been shown to phosphorylate proteins involved in TCR signaling, cytoskeletal reorganization, and IL-4 production. Fyn-deficient mice have greatly decreased numbers of NKT cells and have thymocytes and T cells with compromised responses following Ab crosslinking of their TCRs. Herein we have addressed the role of Fyn in peptide/MHC class II-induced CD4(+) T cell responses. In Fyn-deficient mice, CD4(+) T cells expressing the DO11.10 TCR transgene developed normally, and the number and phenotype of naive and regulatory DO11.10(+)CD4(+) T cells in the periphery were comparable with their wild-type counterparts. Conjugation with chicken OVA peptide 323-339-loaded APCs, and the subsequent proliferation in vitro or in vivo of DO11.10(+) Fyn-deficient CD4(+) T cells, was virtually indistinguishable from the response of DO11.10(+) wild-type CD4(+) T cells. Proliferation of Fyn-deficient T cells was not more dependent on costimulation through CD28. Additionally, we have found that differentiation, in vitro or in vivo, of transgenic CD4(+) Fyn-deficient T cells into IL-4-secreting effector cells was unimpaired, and under certain conditions DO11.10(+) Fyn-deficient CD4(+) T cells were more potent cytokine-producing cells than DO11.10(+) wild-type CD4(+) T cells. These data demonstrate that ablation of Fyn expression does not alter most Ag-driven CD4(+) T cell responses, with the exception of cytokine production, which under some circumstances is enhanced in Fyn-deficient CD4(+) T cells.