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Distinct CD 4 T‐cell effects on primary versus recall CD 8 T‐cell responses during viral encephalomyelitis
Author(s) -
Hwang Mihyun,
Phares Timothy W.,
Hinton David R.,
Stohlman Stephen A.,
Bergmann Cornelia C.,
Min Booki
Publication year - 2015
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12378
Subject(s) - biology , cytotoxic t cell , t cell , immunology , cd8 , interleukin 21 , population , antigen , immune system , in vitro , medicine , genetics , environmental health
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.