title: Simian immunodeficiency virus infects follicular helper CD4 T cells in lymphoid tissues during pathogenic infection of pigtail macaques.
abstract: T follicular helper (Tfh) cells are a specialized subset of memory CD4(+) T cells that are found exclusively within the germinal centers of secondary lymphoid tissues and are important for adaptive antibody responses and B cell memory. Tfh cells do not express CCR5, the primary entry coreceptor for both human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV), and therefore, we hypothesized that these cells would avoid infection. We studied lymph nodes and spleens from pigtail macaques infected with pathogenic strain SIVmac239 or SIVmac251, to investigate the susceptibility of Tfh cells to SIV infection. Pigtail macaque PD-1(high) CD127(low) memory CD4(+) T cells have a phenotype comparable to that of human Tfh cells, expressing high levels of CXCR5, interleukin-21 (IL-21), Bcl-6, and inducible T cell costimulator (ICOS). As judged by either proviral DNA or cell-associated viral RNA measurements, macaque Tfh cells were infected with SIV at levels comparable to those in other CD4(+) memory T cells. Infection of macaque Tfh cells was evident within weeks of inoculation, yet we confirmed that Tfh cells do not express CCR5 or either of the well-known alternative SIV coreceptors, CXCR6 and GPR15. Mutations in the SIV envelope gp120 region occurred in chronically infected macaques but were uniform across each T cell subset investigated, indicating that the viruses used the same coreceptors to enter different cell subsets. Early infection of Tfh cells represents an unexpected focus of viral infection. Infection of Tfh cells does not interrupt antibody production but may be a factor that limits the quality of antibody responses and has implications for assessing the size of the viral reservoir.
authors: Kirby Institute, The University of New South Wales, Sydney, New South Wales, Australia.
authors: Yin
authors: Y
authors: Xu
authors: Chris
authors: C
authors: Weatherall
authors: Michelle
authors: M
authors: Bailey
authors: Sheilajen
authors: S
authors: Alcantara
authors: Robert
authors: R
authors: De Rose
authors: Jerome
authors: J
authors: Estaquier
authors: Kim
authors: K
authors: Wilson
authors: Kazuo
authors: K
authors: Suzuki
authors: Jacques
authors: J
authors: Corbeil
authors: David A
authors: DA
authors: Cooper
authors: Stephen J
authors: SJ
authors: Kent
authors: Anthony D
authors: AD
authors: Kelleher
authors: John
authors: J
authors: Zaunders
mesh_terms: D000818:Animals; D001483:Base Sequence; D016207:Cytokines / Q000276:immunology; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D008221:Lymphoid Tissue / Q000166:cytology / Q000821:virology; D008254:Macaca nemestrina; D008562:Membrane Glycoproteins / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D018709:Statistics, Nonparametric; D006377:T-Lymphocytes, Helper-Inducer / Q000821:virology*; D014759:Viral Envelope Proteins / Q000235:genetics
chemical_list: D016207:Cytokines; D017931:DNA Primers; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus