Cytolytic CD8+ T cells infiltrate germinal centers to limit ongoing HIV replication in spontaneous controller lymph nodes
Collins DR, Hitschfel J, Urbach JM, Mylvaganam GH, Ly NL, Arshad U, Racenet ZJ, Yanez AG, Diefenbach TJ, Walker BD (2023)
Publication Type: Journal article
Publication year: 2023
Journal
Book Volume: 8
Pages Range: eade5872-
Journal Issue: 83
DOI: 10.1126/sciimmunol.ade5872
Abstract
Follicular CD8+ T cells (fCD8) mediate surveillance in lymph node (LN) germinal centers against lymphotropic infections and cancers, but the precise mechanisms by which these cells mediate immune control remain incompletely resolved. To address this, we investigated functionality, clonotypic compartmentalization, spatial localization, phenotypic characteristics, and transcriptional profiles of LN-resident virus-specific CD8+ T cells in persons who control HIV without medications. Antigen-induced proliferative and cytolytic potential consistently distinguished spontaneous controllers from noncontrollers. T cell receptor analysis revealed complete clonotypic overlap between peripheral and LN-resident HIV-specific CD8+ T cells. Transcriptional analysis of LN CD8+ T cells revealed gene signatures of inflammatory chemotaxis and antigen-induced effector function. In HIV controllers, the cytotoxic effectors perforin and granzyme B were elevated among virus-specific CXCR5+ fCD8s proximate to foci of HIV RNA within germinal centers. These results provide evidence consistent with cytolytic control of lymphotropic infection supported by inflammatory recruitment, antigen-specific proliferation, and cytotoxicity of fCD8s.
Involved external institutions
United States (USA) (US)How to cite
APA:
Collins, D.R., Hitschfel, J., Urbach, J.M., Mylvaganam, G.H., Ly, N.L., Arshad, U.,... Walker, B.D. (2023). Cytolytic CD8+ T cells infiltrate germinal centers to limit ongoing HIV replication in spontaneous controller lymph nodes. Science immunology, 8(83), eade5872-. https://dx.doi.org/10.1126/sciimmunol.ade5872
MLA:
Collins, David R., et al. "Cytolytic CD8+ T cells infiltrate germinal centers to limit ongoing HIV replication in spontaneous controller lymph nodes." Science immunology 8.83 (2023): eade5872-.
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