Follicular Regulatory CD8 T Cells Impair the Germinal Center Response in SIV and Ex Vivo HIV Infection

PLoS Pathogens

David N. Levy¹  Shannon M. Miller²  Pamela J. Skinner³  Brodie Miles⁴  Joy M. Folkvord⁵  Elizabeth Connick⁵  Eva G. Rakasz⁶ 

[1] Department of Basic Science, New York University College of Dentistry, New York, United States of America;Department of Immunology and Microbiology, School of Medicine, Anschutz Medical Campus, University of Colorado Denver, Colorado, United States of America;Department of Veterinary and Biomedical Sciences, University of Minnesota, Minnesota, United States of America;Division of Infectious Diseases, Anschutz Medical Campus, University of Colorado Denver, Colorado, United States of America;Division of Infectious Diseases, University of Arizona, Arizona, United States of America;Wisconsin National Primate Research Center, University of Wisconsin-Madison, Wisconsin, United States of America

关键词: Cytotoxic T cells;    T cells;    Tonsils;    HIV;    Macaque;    Rhesus monkeys;    HIV infections;    SIV;   

DOI  :  10.1371/journal.ppat.1005924

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

During chronic HIV infection, viral replication is concentrated in secondary lymphoid follicles. Cytotoxic CD8 T cells control HIV replication in extrafollicular regions, but not in the follicle. Here, we show CXCR5hiCD44hiCD8 T cells are a regulatory subset differing from conventional CD8 T cells, and constitute the majority of CD8 T cells in the follicle. This subset, CD8 follicular regulatory T cells (CD8 TFR), expand in chronic SIV infection, exhibit enhanced expression of Tim-3 and IL-10, and express less perforin compared to conventional CD8 T cells. CD8 TFR modestly limit HIV replication in follicular helper T cells (TFH), impair TFH IL-21 production via Tim-3, and inhibit IgG production by B cells during ex vivo HIV infection. CD8 TFR induce TFH apoptosis through HLA-E, but induce less apoptosis than conventional CD8 T cells. These data demonstrate that a unique regulatory CD8 population exists in follicles that impairs GC function in HIV infection.

【 授权许可】

CC BY