Expansion of HIV-specific T follicular helper cells in chronic HIV infection
Madelene Lindqvist, … , Julian Schulze zur Wiesch, Hendrik Streeck
Madelene Lindqvist, … , Julian Schulze zur Wiesch, Hendrik Streeck
Published August 27, 2012
Citation Information: J Clin Invest. 2012;122(9):3271-3280. https://doi.org/10.1172/JCI64314.
View: Text | PDF
Research Article Article has an altmetric score of 5

Expansion of HIV-specific T follicular helper cells in chronic HIV infection

Abstract

HIV targets CD4 T cells, which are required for the induction of high-affinity antibody responses and the formation of long-lived B cell memory. The depletion of antigen-specific CD4 T cells during HIV infection is therefore believed to impede the development of protective B cell immunity. Although several different HIV-related B cell dysfunctions have been described, the role of CD4 T follicular helper (TFH) cells in HIV infection remains unknown. Here, we assessed HIV-specific TFH responses in the lymph nodes of treatment-naive and antiretroviral-treated HIV-infected individuals. Strikingly, both the bulk TFH and HIV-specific TFH cell populations were significantly expanded in chronic HIV infection and were highly associated with viremia. In particular, GAG-specific TFH cells were detected at significantly higher levels in the lymph nodes compared with those of GP120-specific TFH cells and showed preferential secretion of the helper cytokine IL-21. In addition, TFH cell expansion was associated with an increase of germinal center B cells and plasma cells as well as IgG1 hypersecretion. Thus, our study suggests that high levels of HIV viremia drive the expansion of TFH cells, which in turn leads to perturbations of B cell differentiation, resulting in dysregulated antibody production.

Authors

Madelene Lindqvist, Jan van Lunzen, Damien Z. Soghoian, Bjorn D. Kuhl, Srinika Ranasinghe, Gregory Kranias, Michael D. Flanders, Samuel Cutler, Naomi Yudanin, Matthias I. Muller, Isaiah Davis, Donna Farber, Philip Hartjen, Friedrich Haag, Galit Alter, Julian Schulze zur Wiesch, Hendrik Streeck

×

Figure 2

TFH cells in the lymph node are predominantly effector memory cells and secrete high levels of IL-21.

Options: View larger image (or click on image) Download as PowerPoint
TFH cells in the lymph node are predominantly effector memory cells and ...
(A) Representative flow plots of IFN-γ and IL-21 production of TFH cells in the lymph node. Numbers represent fraction (%) of total CD4 T cells. (B) Frequency of cytokine production dependent on CXCR5 and PD-1 expression in CD4 T cell subsets in the lymph node and periphery. Symbols represent individual samples; horizontal bars represent mean; and error bars show SEM. (C) Definition of memory phenotype of CD4 T cell subsets in the lymph node demonstrated the majority of CXCR5+PD-1hi cells to be effector memory cells. Naive CCR7+CD45RA+, central memory (CM) CCR7+CD45RA–, TEMRA CCR7–CD45RA+, and effector memory (EM) CCR7–CD45RA– (n = 19) cells are shown. In box-and-whisker plots, horizontal bars indicate the medians, boxes indicate 25th to 75th percentiles, and whiskers represent 1.5 times the interquartile distance (Tukey).