Infant T cells are developmentally adapted for robust lung immune responses through enhanced T cell receptor signaling.

Autor:	Thapa P; Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA., Guyer RS; Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA., Yang AY; Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA., Parks CA; Columbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA.; Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA., Brusko TM; Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32611, USA., Brusko M; Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32611, USA., Connors TJ; Department of Pediatrics, Columbia University Irving Medical Center, New York, NY 10032, USA., Farber DL; Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA.; Department of Surgery, Columbia University Irving Medical Center, New York, NY 10032, USA.
Jazyk:	angličtina
Zdroj:	Science immunology [Sci Immunol] 2021 Dec 10; Vol. 6 (66), pp. eabj0789. Date of Electronic Publication: 2021 Dec 10.
DOI:	10.1126/sciimmunol.abj0789
Abstrakt:	Infants require coordinated immune responses to prevent succumbing to multiple infectious challenges during early life, particularly in the respiratory tract. The mechanisms by which infant T cells are functionally adapted for these responses are not well understood. Here, we demonstrated using an in vivo mouse cotransfer model that infant T cells generated greater numbers of lung-homing effector cells in response to influenza infection compared with adult T cells in the same host, due to augmented T cell receptor (TCR)–mediated signaling. Mouse infant T cells showed increased sensitivity to low antigen doses, originating at the interface between T cells and antigen-bearing accessory cells—through actin-mediated mobilization of signaling molecules to the immune synapse. This enhanced signaling was also observed in human infant versus adult T cells. Our findings provide a mechanism for how infants control pathogen load and dissemination, which is important for designing developmentally targeted strategies for promoting immune responses at this vulnerable life stage.
Databáze:	MEDLINE
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