RT Journal Article
T1 Human T-cell receptor inborn errors of immunity shed light on the real-life role of γδ vs αβ T lymphocytes
A1 Marín Marín, Ana Victoria
A1 Chacón Arguedas, Carlos Daniel
A1 Estévez Benito, Ivan
A1 Zarco Cuadrillero, Ángela
A1 Muñoz Ruiz, Miguel
A1 Regueiro González-Barros, José Ramón
AB 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.
PB Elsevier
SN 1937-6448
YR 2025
FD 2025-09-23
LK https://hdl.handle.net/20.500.14352/124897
UL https://hdl.handle.net/20.500.14352/124897
LA eng
NO Ministerio de Ciencia, Innovación y Universidades (España)
NO Comunidad Autónoma de Madrid
NO Asociación Española Contra el Cáncer
NO The Association Against Cancer
NO Fundación FERO
DS Docta Complutense
RD 8 jun 2026