Follicular regulatory T cells impair follicular T helper cells in HIV and SIV infection.
Human and simian immunodeficiency viruses (HIV and SIV) exploit follicular lymphoid regions by establishing high levels of viral replication and dysregulating humoral immunity. Follicular regulatory T cells (TFR) are a recently characterized subset of lymphocytes that influence the germinal centre response through interactions with follicular helper T cells (TFH). Here, utilizing both human and rhesus macaque models, we show the impact of HIV and SIV infection on TFR number and function. We find that TFR proportionately and numerically expand during infection through mechanisms involving viral entry and replication, TGF-β signalling, low apoptosis rates and the presence of regulatory dendritic cells. Further, TFR exhibit elevated regulatory phenotypes and impair TFH functions during HIV infection. Thus, TFR contribute to inefficient germinal centre responses and inhibit HIV and SIV clearance.
Division of Infectious Diseases, Department of Medicine, Anschutz Medical Campus, University of Colorado, Aurora, Colorado 80045, USA.
Brodie
B
Miles
Division of Infectious Diseases, Department of Medicine, Anschutz Medical Campus, University of Colorado, Aurora, Colorado 80045, USA.
Shannon M
SM
Miller
Division of Infectious Diseases, Department of Medicine, Anschutz Medical Campus, University of Colorado, Aurora, Colorado 80045, USA.
Joy M
JM
Folkvord
Division of Infectious Diseases, Department of Medicine, Anschutz Medical Campus, University of Colorado, Aurora, Colorado 80045, USA.
Abigail
A
Kimball
Division of Infectious Diseases, Department of Medicine, Anschutz Medical Campus, University of Colorado, Aurora, Colorado 80045, USA.
Mastooreh
M
Chamanian
Division of Infectious Diseases, Department of Medicine, Anschutz Medical Campus, University of Colorado, Aurora, Colorado 80045, USA.
Amie L
AL
Meditz
Division of Infectious Diseases, Department of Medicine, Anschutz Medical Campus, University of Colorado, Aurora, Colorado 80045, USA.
Tessa
T
Arends
Department of Surgery, School of Medicine, Anschutz Medical Campus, University of Colorado, Aurora, Colorado 80045, USA.
Martin D
MD
McCarter
Department of Basic Science, New York University College of Dentistry, New York, New York 10010, USA.
David N
DN
Levy
Department of Pathology and Laboratory Medicine, Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin 53715, USA.
Eva G
EG
Rakasz
Department of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota 55108, USA.
Pamela J
PJ
Skinner
Division of Infectious Diseases, Department of Medicine, Anschutz Medical Campus, University of Colorado, Aurora, Colorado 80045, USA.
Elizabeth
E
Connick
D000328:Adult; D000368:Aged; D000818:Animals; D002478:Cells, Cultured; D002908:Chronic Disease; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology*; D008253:Macaca mulatta; D008297:Male; D008875:Middle Aged; D014066:Palatine Tonsil / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D055815:Young Adult
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016212:Transforming Growth Factor beta