Fig. 2.

Regulation of SR CD4 T cells during chronic JHM v2.2-1 infection. CD4 and CD8 T cell-dependent virus control leads to immune-mediated demyelination. Myelin debris is drained to the CLN (as a soluble form or cell-associated) where CD11b⁺ myeloid cells present myelin antigen. Activation of SR CD4 T cells is temporally restricted to chronic infection associated with primary demyelination. Following peripheral activation, SR CD4 T cells migrate to the CNS where CD45^hiCD11b⁺ myeloid cells can present myelin antigen to reactive SR CD4 T cells for access to the CNS parenchyma. Nevertheless, Foxp3 Tregs and Tr-1 cells regulate proliferation of SR CD4 T cells in the CLN and CNS respectively, thereby counteracting autoimmune tissue destruction. Altogether, JHM v2.2-1-associated regulatory mechanisms prevent development of autoimmune disease during chronic infection without affecting viral control. OLG: oligodendrocyte.