{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T06:47:46Z","timestamp":1781246866406,"version":"3.54.1"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:00:00Z","timestamp":1738108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontierspartnerships.org"],"crossmark-restriction":true},"short-container-title":["Transpl Int"],"abstract":"<jats:p>The generation of donor-specific antibodies (DSA) requires that alloreactive B cells receive help from follicular helper T (T<jats:sub>FH<\/jats:sub>) cells. Recent works have suggested that \u03b3\u03b4 T cells could contribute to T cell-dependent humoral responses, leading us to investigate their role in DSA generation. Analysis of a cohort of 331 kidney transplant recipients found no relation between the number of circulating \u03b3\u03b4 T cells and the risk to develop DSA. Coculture models demonstrated that activated \u03b3\u03b4 T cells were unable to promote the differentiation of B cells into plasma cells, ruling out that they can be \u201csurrogate\u201d T<jats:sub>FH<\/jats:sub>. In line with this, \u03b3\u03b4 T cells preferentially localized outside the B cell follicles, in the T cell area of lymph nodes, suggesting that they could instead act as \u201cantigen-presenting cell\u201d (APC) to prime \u03b1\u03b2 T<jats:sub>FH<\/jats:sub>. This hypothesis was proven wrong since \u03b3\u03b4 T cells failed to acquire APC functions <jats:italic>in vitro<\/jats:italic>. These findings were validated <jats:italic>in vivo<\/jats:italic> by the demonstration that following transplantation with an allogeneic Balb\/c (H2<jats:sup>d<\/jats:sup>) heart, wild-type and TCR\u03b4KO C57BL\/6 (H2<jats:sup>b<\/jats:sup>) mice developed similar DSA responses, whereas TCR\u03b1KO recipients did not develop DSA. We concluded that the generation of DSA is unfazed by the absence of \u03b3\u03b4 T cells.<\/jats:p>","DOI":"10.3389\/ti.2025.12859","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T13:49:22Z","timestamp":1738158562000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["\u03b3\u03b4 T Cells\u2019 Role in Donor-Specific Antibody Generation: Insights From Transplant Recipients and Experimental 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