title: Persistent Simian Immunodeficiency Virus Infection Causes Ultimate Depletion of Follicular Th Cells in AIDS.
abstract: CD4(+) T follicular helper (Tfh) cells are critical for the generation of humoral immune responses to pathogenic infections, providing help for B cell development, survival, and affinity maturation of Abs. Although CD4(+) Tfh cells are reported to accumulate in HIV or SIV infection, we found that germinal center Tfh cells, defined in this study as CXCR5(+)PD-1(HIGH)CD4(+) T cells, did not consistently accumulate in chronically SIV-infected rhesus macaques compared with those infected with less pathogenic simian HIV, vaccinated and SIVmac-challenged, or SIVmac-infected Mamu-A*01(+) macaques, all of which are associated with some control of virus replication and slower disease progression. Interestingly, CXCR5(+)PD-1(HIGH) Tfh cells in lymphoid tissues were eventually depleted in macaques with AIDS compared with the other cohorts. Chronic activation and proliferation of CXCR5(+)PD-1(HIGH) Tfh were increased, but PD-L2 expression was downregulated on B cells, possibly resulting in germinal center Tfh cell apoptosis. Together, these findings suggest that changes in CXCR5(+)PD-1(HIGH) Tfh cells in lymph nodes correlate with immune control during infection, and their loss or dysregulation contribute to impairment of B cell responses and progression to AIDS.
authors.affiliation: Tulane National Primate Research Center, Tulane University School of Medicine, Covington, LA 70433.
authors.forename: Huanbin
authors.initials: H
authors.lastname: Xu
authors.affiliation: Tulane National Primate Research Center, Tulane University School of Medicine, Covington, LA 70433.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Tulane National Primate Research Center, Tulane University School of Medicine, Covington, LA 70433.
authors.forename: Naomi
authors.initials: N
authors.lastname: Malam
authors.affiliation: Tulane National Primate Research Center, Tulane University School of Medicine, Covington, LA 70433.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Lackner
authors.affiliation: Tulane National Primate Research Center, Tulane University School of Medicine, Covington, LA 70433 rveazey@tulane.edu.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Veazey
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000378:metabolism / Q000821:virology; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002478:Cells, Cultured; D018920:Coculture Techniques; D005434:Flow Cytometry; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism / Q000821:virology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008253:Macaca mulatta / Q000276:immunology* / Q000821:virology; D018613:Microscopy, Confocal; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology / Q000378:metabolism; D054380:Receptors, CXCR5 / Q000276:immunology / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D014779:Virus Replication / Q000276:immunology
chemical_list: D061026:Programmed Cell Death 1 Receptor; D054380:Receptors, CXCR5