RT Journal Article
T1 PLA2G1B is involved in CD4 anergy and CD4 lymphopenia in HIV-infected patients.
A1 Pothlichet, Julien
A1 Rose, Thierry
A1 Bugault, Florence
A1 Jeammet, Louise
A1 Meola, Annalisa
A1 Haouz, Ahmed
A1 Saul, Frederick
A1 Geny, David
A1 Alcami, José
A1 Ruiz-Mateos, Ezequiel
A1 Teyton, Luc
A1 Lambeau, Gérard
A1 Thèze, Jacques
K1 AIDS/HIV
K1 Cytokines
K1 Immunology
K1 Lipid rafts
K1 T cells
AB The precise mechanism leading to profound immunodeficiency of HIV-infected patients is still only partially understood. Here, we show that more than 80% of CD4+ T cells from HIV-infected patients have morphological abnormalities. Their membranes exhibited numerous large abnormal membrane microdomains (aMMDs), which trap and inactivate physiological receptors, such as that for IL-7. In patient plasma, we identified phospholipase A2 group IB (PLA2G1B) as the key molecule responsible for the formation of aMMDs. At physiological concentrations, PLA2G1B synergized with the HIV gp41 envelope protein, which appears to be a driver that targets PLA2G1B to the CD4+ T cell surface. The PLA2G1B/gp41 pair induced CD4+ T cell unresponsiveness (anergy). At high concentrations in vitro, PLA2G1B acted alone, independently of gp41, and inhibited the IL-2, IL-4, and IL-7 responses, as well as TCR-mediated activation and proliferation, of CD4+ T cells. PLA2G1B also decreased CD4+ T cell survival in vitro, likely playing a role in CD4 lymphopenia in conjunction with its induced IL-7 receptor defects. The effects on CD4+ T cell anergy could be blocked by a PLA2G1B-specific neutralizing mAb in vitro and in vivo. The PLA2G1B/gp41 pair constitutes what we believe is a new mechanism of immune dysfunction and a compelling target for boosting immune responses in HIV-infected patients.
YR 2020
FD 2020
LK http://hdl.handle.net/10668/15607
UL http://hdl.handle.net/10668/15607
LA en
DS RISalud
RD Apr 8, 2025