CCR 5 deficiency impairs CD 4+ T-cell memory responses and antigenic sensitivity through increased ceramide synthesis

A. Martín-Leal, R. Blanco, J. Casas, M. E. Sáez, E. Bovolenta, I. de Rojas, C. Drechsler, L.M. Real, G. Fabriàs, A. Ruiz, M. Castro, W.W. Schamel, B. Alarcón, H.M. Van Santen, S. Mañes

EMBO Journal Vol. 39, nº. 15, pp. e104749-1 - e104749-19

Summary:
CCR 5 is not only a coreceptor for HIV -1 infection in CD 4+ T cells, but also contributes to their functional fitness. Here, we show that by limiting transcription of specific ceramide synthases, CCR 5 signaling reduces ceramide levels and thereby increases T-cell antigen receptor (TCR ) nanoclustering in antigen-experienced mouse and human CD 4+ T cells. This activity is CCR 5-specific and independent of CCR 5 co-stimulatory activity. CCR 5-deficient mice showed reduced production of high-affinity class-switched antibodies, but only after antigen rechallenge, which implies an impaired memory CD 4+ T-cell response. This study identifies a CCR 5 function in the generation of CD 4+ T-cell memory responses and establishes an antigen-independent mechanism that regulates TCR nanoclustering by altering specific lipid species.

Keywords: ccr5[delta]32; humoral response; membrane phase; sphingolipid;T-cell receptor

JCR Impact Factor and WoS quartile: 11,598 - Q1 (2020); 11,400 - Q1 (2022)

DOI reference: https://doi.org/10.15252/embj.2020104749

Published on paper: August 2020.

Published on-line: June 2020.

Citation:
A. Martín-Leal, R. Blanco, J. Casas, M. E. Sáez, E. Bovolenta, I. de Rojas, C. Drechsler, L.M. Real, G. Fabriàs, A. Ruiz, M. Castro, W.W. Schamel, B. Alarcón, H.M. Van Santen, S. Mañes, CCR 5 deficiency impairs CD 4+ T-cell memory responses and antigenic sensitivity through increased ceramide synthesis. EMBO Journal. Vol. 39, nº. 15, pp. e104749-1 - e104749-19, August 2020. [Online: June 2020]