Author(s)

Behrouz Moemeni^1,2, Nathalie Vacaresse¹, Marina Vainder¹, Michael E. Wortzman², Tania H. Watts², André Veillette³, Thomas F. Gajewski⁴, Michael Julius^1,2

¹Sunnybrook Research Institute, Toronto, Canada.
²Department of Immunology, University of Toronto, Toronto, Canada.
³Laboratory of Molecular Oncology, Clinical Research Institute of Montreal, Montreal, Canada.
⁴Department of Pathology, University of Chicago, Chicago, IL, USA.

Genomic disruption of Fyn has not been associated with an immune-deficient phenotype, notwithstanding the profound impairment in IL-2 production by T cells derived from Fyn-deficient animals observed in vitro. The results presented demonstrate that Fyn deficient animals succumb to influenza infection ahead of the protective expansion of lung infiltrating T cells and viral clearance observed in wild-type hosts. Formal proof that Fyn-dependent IL-2 production mediates T cell expansion in vivo is provided using a model of T cell induced enteropathy. Specifically, Fyn deficient naive T cells do not induce colitis in SCID animals due to their lack of expansion, and Fyn re-expression rescues both IL-2 production and its capacity to support in vivo expansion leading to colitis. These results reconcile the obligatory role of Fyn in T cell activation and autocrine IL-2 supported growth; and underscore the mechanism through which its function is integrated with and regulated by Lck.

Fyn, Lck, TcR Signaling, Immunity, Autoimmunity

Moemeni, B. , Vacaresse, N. , Vainder, M. , Wortzman, M. , Watts, T. , Veillette, A. , Gajewski, T. and Julius, M. (2015) Fyn Expression Predicates Both Protective Immunity and Onset of Autoimmunity. Open Journal of Immunology, 5, 244-259. doi: 10.4236/oji.2015.55020.