Early growth response genes -2 and -3 are required for naïve T cell activation and primary response against virus infection (P1150)

Abstract

T cells robustly respond to virus infection. Egr-2 and -3 are induced in both naïve and tolerant T cells (PMC2652694, PMID15585857, PMID15834410). The deficiency of Egr-2 and -3 specifically in B and T cells results in autoimmunity (PMID23021953). It is however unknown whether they also play roles in protective immmunoresponses. We have now shown that Egr-2 and -3 are required for naïve T cell activation in response to virus infection. Defect in Egr-2 and -3 restrains the IL-2 production and the expansion of viral specific CD4 and CD8 T cells, leading to the development of chronic infection despite active phenotypes and excessive production of IFNg. The induced Egr-2 and -3 in naïve T cells are essential for the maintenance of optimal AP-1 activation and IL-2 production leading to the rapid expansion of viral specific T cells. In addition to the proliferation of viral specific T cells, Egr-2 and -3 control the production of inflammatory cytokines and the activation phenotypes of viral specific T cells at early stages of infection to limit inflammatory pathology and build a pool of responding T cells for a robust anti-viral effect with minimum immunopathology. The functions of Egr-2 and -3 are limited in naïve T cells in primary immunoresponses and are not involved in the development of the memory pool and secondary responses. In conclusion, in addition to the maintenance of immunohomeostasis, Egr-2 and -3 are important to primary immune responses against virus infection.