title: Early lymphoid responses and germinal center formation correlate with lower viral load set points and better prognosis of simian immunodeficiency virus infection.
abstract: We have investigated the dynamics of germinal center (GC) formation in lymphoid tissues following acute SIV infection. SIV induces a marked follicular hyperplasia, associated with an aberrant accumulation of nonproliferating T follicular helper cells within GCs, but with an abundance of cells producing IL-21, demonstrating that the mechanisms involved for these two events appear independent. IL-21-stimulated T follicular helper cells are considered a critical element for GC formation, a physiological process that seems dysregulated and excessive during HIV/SIV infection, contributing to lymphoid pathogenesis. However, the data suggest that the kinetics by which such GCs are formed may be an important predictor of the host-pathogen equilibrium, as early GC hyperplasia was associated with better control of viral replication. In contrast, monkeys undergoing fast disease progression upon infection exhibited an involution of GCs without local IL-21 production in GCs. These results provide important clues regarding GC-related hyperimmune responses in the context of disease progression within various individuals during HIV/SIV infection and may open novel therapeutic avenues to limit lymphoid dysfunction, postinfection.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322; Division of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329; and.
authors.forename: Jung Joo
authors.initials: JJ
authors.lastname: Hong
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322; Division of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329; and.
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Amancha
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322; Division of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329; and.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Rogers
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322; Division of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329; and.
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Courtney
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037.
authors.forename: Colin
authors.initials: C
authors.lastname: Havenar-Daughton
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037.
authors.forename: Shane
authors.initials: S
authors.lastname: Crotty
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322; Division of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329; and.
authors.forename: Aftab A
authors.initials: AA
authors.lastname: Ansari
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322; Division of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329; and.
authors.forename: Francois
authors.initials: F
authors.lastname: Villinger
mesh_terms: D000818:Animals; D018951:Antigens, CD20 / Q000276:immunology / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D018858:Germinal Center / Q000276:immunology* / Q000821:virology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006965:Hyperplasia / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D007378:Interleukins / Q000276:immunology / Q000378:metabolism; D019394:Ki-67 Antigen / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology / Q000821:virology; D008221:Lymphoid Tissue / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008253:Macaca mulatta; D008856:Microscopy, Fluorescence; D011379:Prognosis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000175:diagnosis / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D019562:Viral Load; D000098546:Interleukin-21
chemical_list: D018951:Antigens, CD20; D017252:CD3 Complex; D007378:Interleukins; D019394:Ki-67 Antigen; D000098546:Interleukin-21