title: Chronic HIV-1 Infection Impairs Superantigen-Induced Activation of Peripheral CD4+CXCR5+PD-1+ Cells, With Relative Preservation of Recall Antigen-Specific Responses.
abstract: Peripheral CD4+CXCR5+PD-1+ T cells are a putative circulating counterpart to germinal center T follicular helper (TFH) cells. They show both phenotypic and functional similarities to TFH cells, which provide necessary help for the differentiation of B cells to antibody-secreting plasmablasts. In this study, we evaluated the frequency, phenotypes, and responses of peripheral TFH-like (pTFH) cells to superantigen and recall antigen stimulation in 10 healthy and 34 chronically infected treatment-naive HIV-1+ individuals. There was no difference in the frequency of pTFH cells between HIV+ and HIV- individuals. Surface expression of ICOS, but not CD40L, was higher on pTFH cells at baseline in HIV+ individuals. Compared with HIV- individuals, pTFH cells from HIV+ individuals had decreased maximal expression of ICOS and CD40L in response to in vitro superantigen stimulation. This decreased response did not correlate with viral control, CD4 T-cell count, duration of infection, or the degree of neutralizing antibody breadth. Despite a decreased maximal response, pTFH responses to HIV Gag and tetanus toxoid recall antigens were preserved.
authors: *Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN; †Flow Cytometry Shared Resource, Vanderbilt University Medical Center, Nashville, TN; ‡Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN; and §Seattle Biomedical Research Institute, Seattle, WA.
authors: Katherine J
authors: KJ
authors: Nicholas
authors: David K
authors: DK
authors: Flaherty
authors: Rita M
authors: RM
authors: Smith
authors: D Noah
authors: DN
authors: Sather
authors: Spyros A
authors: SA
authors: Kalams
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D023201:CD40 Ligand / Q000032:analysis; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein / Q000032:analysis; D008213:Lymphocyte Activation; D061026:Programmed Cell Death 1 Receptor / Q000032:analysis*; D054380:Receptors, CXCR5 / Q000032:analysis*; D018089:Superantigens / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*
chemical_list: C095085:CXCR5 protein, human; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D054380:Receptors, CXCR5; D018089:Superantigens; D023201:CD40 Ligand