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Following congenital cytomegalovirus infection (cCMV), V\u03b41 T cells have been shown to expand, differentiate, and upregulate cytotoxic mediators, but display markedly restricted \u03b3\u03b4TCR diversity compared to CMV-infected adults. Early fetal \u03b3\u03b4 T cells are biased toward rapid effector function and comprise a distinct ontological \u201clayer\u201d that can be distinguished from late gestation \u03b3\u03b4 T cells based on TCR characteristics. To better understand the contribution of fetal \u03b3\u03b4 T cells to antiviral defense in utero, we analyzed \u03b3\u03b4 T cells from cCMV+ and uninfected neonates in Uganda using flow cytometry and paired single-cell RNA and TCR sequencing. We observed that in cCMV+ neonates, \u03b3\u03b4 T cells clonally proliferate and differentiate into a uniform population of cytotoxic effectors. The expanded V\u03b41 population is comprised of diverse clonotypes with broad V\u03b3 chain usage, with a striking correlation between expansion and publicity. Overall, \u03b3\u03b4TCR repertoires of cCMV+ infants have shorter CDR3 lengths and fewer N additions, suggesting they derive from early fetal progenitor cells. In cCMV+ infants, most cells with fetal \u03b3\u03b4TCR characteristics are effector-differentiated, whereas in uninfected infants, such cells are rare and predominantly na\u00efve. Together, these findings demonstrate that cCMV infection drives an oligoclonal expansion of highly cytotoxic effector \u03b3\u03b4 T cells with fetal-like TCR features, illustrating how the developing immune system prioritizes broad reactivity and rapid effector function over specificity.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag099","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T09:49:23Z","timestamp":1781516963000},"source":"Crossref","is-referenced-by-count":1,"title":["Congenital cytomegalovirus infection drives oligoclonal expansion of cytotoxic \u03b3\u03b4 T cells from early fetal progenitors"],"prefix":"10.1093","volume":"215","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3185-6069","authenticated-orcid":false,"given":"Justine","family":"Levan","sequence":"first","affiliation":[{"name":"Department of Medicine, University of California, San Francisco , San Francisco, CA,","place":["United 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