Abstract
T follicular helper cells (TFh) are key components of the adaptive immune system; they are primarily found in germinal centers (GCs) where their interaction with B cells supports humoral immune responses and efficient antibody production. They are defined by the expression of CXC receptor 5, program death-1, ICOS, and secretion of IL-21. Their differentiation is regulated by B-cell lymphoma 6. The relationship and function of circulating TFh to bona fide TFh resident in the GC is much debated. HIV infection impacts the TFh response with evidence of aberrant TFh function observed in acute and chronic infection. Effective TFh responses are associated with the development of broadly neutralizing antibody responses to HIV and may be important for viral control. In addition, TFh are preferentially infected and act as a key reservoir for latent HIV infection. This review explores recent developments in our understanding of TFh differentiation, regulation, function, and the relationship between cTFh and those in GCs, and the complex interaction between TFh and HIV infection.
Highlights
Optimal immune function requires effective communication between all arms of the immune system
This review aims to summarize the current data and recent advances in our understanding of the role of T follicular helper cells (TFh) in HIV infection, with particular emphasis on the phenotypic and functional differences between germinal centers (GCs) and peripheral-circulating TFh cells
TFh dysregulation in HIV infection has been well characterized. Whether these cells are preferentially infected within GCs and remain as latent reservoirs still requires further investigation
Summary
Optimal immune function requires effective communication between all arms of the immune system. TFh cells play a significant role in supporting B cell activation and antibody production during the humoral immune response They are critical for B cell support, somatic hypermutation (SHM), and antibody class switching [2]. Epigenetic changes which support TFh differentiation have been shown to be important for resolution of LCMV infections [7] These observations support the role of TFh cells in the development of effective pathogenspecific antibody responses to chronic viral infections. The interplay between HIV infection and TFh cells is complex, with evidence supporting dysregulation of TFh function by HIV itself and that the frequency of TFh subsets positively correlates with effective humoral responses to HIV, as measured by the development broadly neutralizing antibodies (BNAbs) [8]. This review aims to summarize the current data and recent advances in our understanding of the role of TFh in HIV infection, with particular emphasis on the phenotypic and functional differences between GC and peripheral-circulating TFh cells (pTFh)
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