CCR5 deficiency impairs CD4+ T cell memory responses and antigenic sensitivity through increased ceramide synthesis

ABSTRACT: CCR5 is not only a coreceptor for HIV-1 infection in CD4+ T cells, but also contributes to their functional fitness. Here we show that by limiting transcription of specific ceramide synthases, CCR5 signaling reduces ceramide levels and thereby increases T cell antigen receptor (TCR) nanoclustering in antigen-experienced mouse and human CD4+ T cells. This activity is CCR5-specific, and independent of CCR5 costimulatory activity. CCR5-deficient mice showed reduced production of high affinity class-switched antibodies, but only after antigen rechallenge, which implies an impaired memory CD4+ T cell response. This study identifies a CCR5 function in the generation of CD4+ T cell memory responses, and establishes an antigen-independent mechanism that regulates TCR nanoclustering by altering specific lipid species.

SUBMITTER: Dr. Ana Martín-Leal 

PROVIDER: S-SCDT-EMBOJ-2020-104749 | biostudies-other |

REPOSITORIES: biostudies-other