Distinct CD4 T‐cell effects on primary versus recall CD8 T‐cell responses during viral encephalomyelitis. Issue 3 (March 2015)

• Record Type: Journal Article
• Authors: Hwang, Mihyun; Phares, Timothy W.; Hinton, David R.; Stohlman, Stephen A.; Bergmann, Cornelia C.; Min, Booki
• Is Part Of: Immunology. Volume 144:Issue 3(2015:Mar.)
• Page Start: 374
• Page End: 386
• Publication Date: 2015-03
• Subjects: Immunology -- Periodicals
• DOI: 10.1111/imm.12378
• Languages: English
• ISSNs: 0019-2805

Abstract

<abstract abstract-type="main" id="imm12378-abs-0001"> <title>Summary</title> <p>CD4 T‐cell help is not a universal requirement for effective primary CD8 T cells but is essential to generate memory CD8 T cells capable of recall responses. This study examined how CD4 T cells affect primary and secondary anti‐viral CD8 T‐cell responses within the central nervous system (CNS) during encephalomyelitis induced by sublethal gliatropic coronavirus. CD4 T‐cell depletion before infection did not impair peripheral expansion, interferon‐<italic>γ</italic> production, CNS recruitment or initial CNS effector capacity of virus‐specific CD8 T cells <italic>ex vivo</italic>. Nevertheless, impaired virus control in the absence of CD4 T cells was associated with gradually diminished CNS CD8 T‐cell interferon‐<italic>γ</italic> production. Furthermore, within the CD8 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 CD8 T cells to reduce viral load in CD4‐depleted mice reverted the recipient CNS CD8 T‐cell phenotype to that in wild‐type control mice. However, memory CD8 T cells primed without CD4 T cells and transferred into infected CD4‐sufficient recipients expanded less efficiently and were not sustained in the CNS, contrasting with their helped counterparts. These data suggest that CD4 T cells are dispensable for initial expansion, CNS recruitment and differentiation of primary resident memory CD8 T cells as long as the duration of antigen exposure is limited. By contrast, CD4 T cells are essential to prolong primary CD8 T‐cell function in the CNS and imprint memory CD8 T cells for recall responses.</p> </abstract>