Distinct CD 4 T‐cell effects on primary versus recall CD 8 T‐cell responses during viral encephalomyelitis

Summary CD 4 T‐cell help is not a universal requirement for effective primary CD 8 T cells but is essential to generate memory CD 8 T cells capable of recall responses. This study examined how CD 4 T cells affect primary and secondary anti‐viral CD 8 T‐cell responses within the central nervous system ( CNS ) during encephalomyelitis induced by sublethal gliatropic coronavirus. CD 4 T‐cell depletion before infection did not impair peripheral expansion, interferon‐ γ production, CNS recruitment or initial CNS effector capacity of virus‐specific CD 8 T cells ex vivo . Nevertheless, impaired virus control in the absence of CD 4 T cells was associated with gradually diminished CNS CD 8 T‐cell interferon‐ γ production. Furthermore, within the CD 8 T‐cell population short‐lived effector cells were increased and memory precursor effector cells were significantly decreased, consistent with higher T‐cell turnover. Transfer of memory CD 8 T cells to reduce viral load in CD 4‐depleted mice reverted the recipient CNS CD 8 T‐cell phenotype to that in wild‐type control mice. However, memory CD 8 T cells primed without CD 4 T cells and transferred into infected CD 4‐sufficient recipients expanded less efficiently and were not sustained in the CNS , contrasting with their helped counterparts. These data suggest that CD 4 T cells are dispensable for initial expansion, CNS recruitment and differentiation of primary resident memory CD 8 T cells as long as the duration of antigen exposure is limited. By contrast, CD 4 T cells are essential to prolong primary CD 8 T‐cell function in the CNS and imprint memory CD 8 T cells for recall responses.