Abstract

Mouse, non-human primate (NHP) and human Tfh cells share phenotypic, functional and molecular programs which are regulated by local signals and spatiotemporal factors. Chronic HIV/SIV infection results in accumulation of Tfh, germinal center (GC) B cells and circulating virus-specific immunoglobulins in some subjects. However, most HIV/SIV infected subjects do not mount broadly neutralizing antibodies, pointing to functional defects in Tfh cells in chronic HIV/SIV infection. The susceptibility of particular CD4 T cells populations to HIV/SIV infection within lymph nodes notably impacts upon the dynamics of Tfh-GC B cell interactions. Some circulating CD4 T cells share certain characteristics with Tfh cells, however their direct origin from GC Tfh cells is not clear. There are many ways in which HIV and SIV influence the complex signals and mechanisms regulating the development of Tfh cells and their interactions with GC B cells. Understanding the biology of Tfh cells will be necessary to appropriately recruit these cells during vaccination with the goal of stimulating a more broad and potent neutralizing antibody response.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI005015-17
Application #
9770214
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
17
Fiscal Year
2018
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
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  Publications

Paris, Robert M; Milagres, Lucimar G; Moysi, Eirini et al. (2017) Lower Baseline Germinal Center Activity and Preserved Th1 Immunity Are Associated With Hepatitis B Vaccine Response in Treated HIV Infection. Pathog Immun 2:66-88
Ferrando-Martinez, Sara; De Pablo-Bernal, Rebeca S; De Luna-Romero, Marta et al. (2017) Thymic Function Failure Is Associated With Human Immunodeficiency Virus Disease Progression. Clin Infect Dis 64:1191-1197
Coates, Emily E; Costner, Pamela J; Nason, Martha C et al. (2017) Lymph Node Activation by PET/CT Following Vaccination With Licensed Vaccines for Human Papillomaviruses. Clin Nucl Med 42:329-334
Wheatley, Adam K; Whittle, James R R; Lingwood, Daniel et al. (2015) H5N1 Vaccine-Elicited Memory B Cells Are Genetically Constrained by the IGHV Locus in the Recognition of a Neutralizing Epitope in the Hemagglutinin Stem. J Immunol 195:602-10
Prentice, Heather A; Tomaras, Georgia D; Geraghty, Daniel E et al. (2015) HLA class II genes modulate vaccine-induced antibody responses to affect HIV-1 acquisition. Sci Transl Med 7:296ra112
Liang, Frank; Ploquin, Aurélie; Hernández, José DelaO et al. (2015) Dissociation of skeletal muscle for flow cytometric characterization of immune cells in macaques. J Immunol Methods 425:69-78
Francica, Joseph R; Sheng, Zizhang; Zhang, Zhenhai et al. (2015) Analysis of immunoglobulin transcripts and hypermutation following SHIV(AD8) infection and protein-plus-adjuvant immunization. Nat Commun 6:6565
Yamamoto, Takuya; Lynch, Rebecca M; Gautam, Rajeev et al. (2015) Quality and quantity of TFH cells are critical for broad antibody development in SHIVAD8 infection. Sci Transl Med 7:298ra120
Petrovas, Constantinos; Koup, Richard A (2014) T follicular helper cells and HIV/SIV-specific antibody responses. Curr Opin HIV AIDS 9:235-41
Boswell, Kristin L; Paris, Robert; Boritz, Eli et al. (2014) Loss of circulating CD4 T cells with B cell helper function during chronic HIV infection. PLoS Pathog 10:e1003853

Showing the most recent 10 out of 32 publications