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oai:docta.ucm.es:20.500.14352/1248972025-10-14T23:46:37Zcom_20.500.14352_14col_20.500.14352_15

Human T-cell receptor inborn errors of immunity shed light on the real-life role of γδ vs αβ T lymphocytes Marín Marín, Ana Victoria Chacón Arguedas, Carlos Daniel Estévez Benito, Ivan Zarco Cuadrillero, Ángela Muñoz Ruiz, Miguel Regueiro González-Barros, José Ramón 612.017 Inmunología 2412 Inmunología T lymphocytes are critical components of adaptive immunity. They are involved, together with other leucocytes, in defense against pathogens, including viruses, bacteria, fungi and parasites. Mature T cells include two subsets, αβ and γδ, depending on the variable T-cell receptor (TCR) expressed on their surface. αβ T cells, the largest subset in blood, are well characterized in terms of their functions in defense against infections. Their central role in protective immunity is dramatically clear in rare human inborn errors of immunity (IEI) causing selective αβ T-cell lymphopenia. Such defects frequently associate to early-onset health-threatening infections and autoimmunity (rather than cancer) and require hematopoietic stem cell transplantation for survival. γδ T-cell function, by contrast, is still not well understood, as we review here. Human IEI affecting several invariant and variable TCR chains (TCRIEI) have been reported, in some cases with a different impact in αβ vs γδ T-cell numbers. By comparing them, we show that clinical severity, as a proxy of importance for survival, associates with the absence of αβ T cells, irrespectively of γδ T-cell numbers. Several species and animal knock-out models which naturally or artificially lack γδ T cells support this contention. Thus, TCRIEI teach us that αβ T cells are crucial for defense against infections, whereas γδ T cells may have a comparatively marginal role in real-life human immunity. Ministerio de Ciencia, Innovación y Universidades (España) Comunidad Autónoma de Madrid Asociación Española Contra el Cáncer The Association Against Cancer Fundación FERO Depto. de Inmunología, Oftalmología y ORL Fac. de Medicina TRUE inpress 2025-10-14T12:20:14Z 2025-10-14T12:20:14Z 2025-09-23 journal article CVoR https://hdl.handle.net/20.500.14352/124897 1937-6448 10.1016/bs.ircmb.2025.08.004 eng MICIU PID2021-125501OB-I00 RED2022-134750-T PID2022-139095OA-I00 PID2024-155827OB-I00 P2022/BMD-7278 PR38/21-13 ANTICIPA-CM AECC PROYE20084REGU restricted access application/pdf Elsevier