|Title||Inadequate T follicular cell help impairs B cell immunity during HIV infection.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Cubas RA, Mudd JC, Savoye A-L, Perreau M, van Grevenynghe J, Metcalf T, Connick E, Meditz A, Freeman GJ, Abesada-Terk G, Jacobson JM, Brooks AD, Crotty S, Estes JD, Pantaleo G, Lederman MM, Haddad EK|
The majority of HIV-infected individuals fail to produce protective antibodies and have diminished responses to new immunizations. We report here that even though there is an expansion of follicular helper T (TFH) cells in HIV-infected individuals, the cells are unable to provide adequate B cell help. We found a higher frequency of programmed cell death ligand 1 (PD-L1)(+) germinal center B cells from lymph nodes of HIV-infected individuals suggesting a potential role for PD-1-PD-L1 interaction in regulating TFH cell function. In fact, we show that engagement of PD-1 on TFH cells leads to a reduction in cell proliferation, activation, inducible T-cell co-stimulator (ICOS) expression and interleukin-21 (IL-21) cytokine secretion. Blocking PD-1 signaling enhances HIV-specific immunoglobulin production in vitro. We further show that at least part of this defect involves IL-21, as addition of this cytokine rescues antibody responses and plasma cell generation in vitro. Our results suggest that deregulation of TFH cell-mediated B cell help diminishes B cell responses during HIV infection and may be related to PD-1 triggering on TFH cells. These results demonstrate a role for TFH cell impairment in HIV pathogenesis and suggest that enhancing their function could have a major impact on the outcome and control of HIV infection, preventing future infections and improving immune responses to vaccinations.
|Alternate Journal||Nat. Med.|
Inadequate T follicular cell help impairs B cell immunity during HIV infection.