Inadequate T follicular cell help impairs B cell immunity during HIV infection

Rafael A Cubas, Joseph C Mudd, Anne-Laure Savoye, Matthieu Perreau, Julien van Grevenynghe, Talibah Metcalf, Elizabeth Connick, Amie Meditz, Gordon J Freeman, Guillermo Abesada-TerkJr, Jeffrey M Jacobson, Ari D Brooks, Shane Crotty, Jacob D Estes, Giuseppe Pantaleo, Michael M Lederman & Elias K Haddad. Nat Med. (2013)19, 494-499.

Speaker: Pei-Chi Chen (陳佩琪)                                Time : 14:10~15:00, October 9, 2013

Commentator: Dr. Bei-Chang Yang (楊倍昌 老師)    Place: Room 601

Abstract

One of the hallmarks of HIV infection is a progressive dysfunction of the humoral immune response, but the underlying mechanism remains unclear. Since B cells themselves are not targets for HIV, it has been suggested that the massive infection and depletion of CD4⁺ T cells, which are required for the induction of high-affinity antibody responses and the formation of long-lived B cell memory, may play a crucial role in the profound defects of the B cell function (1). In this study, Cubas et al. focused on investigating the interaction between follicular helper T (T_FH) cells and germinal center B cells and suggested a new mechanism for the humoral immune dysfunction in HIV infection. The result showed that there is an expansion of T_FH and germinal center B cells in the lymph node of HIV-infected patient compared to healthy control. However, the concentration of IgG under coculture system of HIV⁺ lymph node is lower than HIV^- lymph node. The authors discovered that the T_FH cells from HIV-infected and uninfected lymph node observed similar phenotype and cytokine production, but the function of T_FH is indeed altered because of the higher programmed cell death ligand 1 (PD-L1) expression in germinal center B cell of HIV⁺ lymph node. Under PD-1-PD-L1 interaction, T_FH cells had changed in behavior that depressed T-cell co-stimulator (ICOS) expression, lowering IL-21 stimulation, and as a result B cell antibody production was inhibited (2). Moreover, supplementation of IL-21 or blocking PD-1 pathway could restore HIV-specific T_FH-mediated B cell responses by enhancing antibody production. In conclusion, the altered interaction between T_FH cells and germinal center B cells is responsible for diminished B cell antibody production during HIV infection.

References

1. Moir S., Fauci A.S. (2009) B cells in HIV infection and disease. Nat Rev Immunol. 9, 235-245.
2. Tangye S.G., Ma C.S., Brink R., Deenick E.K. (2013) The good, the bad and the ugly-T_FH cells in human health and disease. Nat Rev Immunol. 13, 412-426.