2026-06-14T03:42:06Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/108592024-11-28T16:45:31Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19609col_20.500.12105_16958col_20.500.12105_16961

00925njm 22002777a 4500 dc Pothlichet, Julien author Rose, Thierry author Bugault, Florence author Jeammet, Louise author Meola, Annalisa author Haouz, Ahmed author Saul, Frederick author Geny, David author Ruiz-Mateos, Ezequiel author Teyton, Luc author Lambeau, Gérard author Thèze, Jacques author Alcamí, José author 2020-06-01 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. J Clin Invest. 2020 Jun 1;130(6):2872-2887. 10.1172/JCI131842 1558-8238 The Journal of clinical investigation 32436864 http://hdl.handle.net/20.500.12105/10859 PLA2G1B is involved in CD4 anergy and CD4 lymphopenia in HIV-infected patients