T follicular helper cells and HIV/SIV-specific antibody responses

Abstract

Here, we describe recent data on the characterization of follicular helper CD4 T cells (Tfh) and the dynamics of Tfh-B-cell interactions in HIV and simian immunodeficiency virus (SIV) infection and discuss important aspects of these interactions that need to be addressed in order to design more effective vaccines that elicit broadly neutralizing antibodies. Mouse, nonhuman primate (NHP) and human Tfh cells share phenotypic, functional and molecular programs, which are regulated by local signals and spatiotemporal parameters. Chronic HIV/SIV infection results in accumulation of Tfh, germinal center B cells and circulating virus-specific immunoglobulins in some individuals. However, most HIV/SIV-infected individuals do not mount broadly neutralizing antibodies, pointing to functional defects in Tfh cells in chronic HIV/SIV infection. The susceptibility of particular CD4 T-cell populations to HIV/SIV infection within lymph nodes notably impacts upon the dynamics of Tfh-germinal center B-cell interactions. Some circulating CD4 T cells share certain characteristics with Tfh cells, however, their direct origin from germinal center 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 germinal center 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.