In utero human cytomegalovirus infection expands NK-like FcγRIII+ CD8+ T cells that mediate Fc antibody functions.

Autor:	Semmes EC; Duke Human Vaccine Institute, Duke University, Durham, United States of America., Nettere DR; Medical Scientist Training Program, Duke University, Durham, United States of America., Nelson AN; Duke Human Vaccine Institute, Duke University, Durham, United States of America., Hurst JH; Division of Infectious Diseases, Department of Pediatrics, Duke University, Durham, United States of America., Cain DW; Duke Human Vaccine Institute, Duke University, Durham, United States of America., Burt TD; Children's Health and Discovery Initiative, Duke University, Durham, United States of America., Kurtzberg J; Children's Health and Discovery Initiative, Duke University, Durham, United States of America., Reeves RK; Department of Surgery, Duke University, Durham, United States of America., Coyne CB; Duke Human Vaccine Institute, Duke University, Durham, United States of America., Fouda GG; Duke Human Vaccine Institute, Duke University, Durham, United States of America., Pollara J; Duke Human Vaccine Institute, Duke University, Durham, United States of America., Permar SR; Duke Human Vaccine Institute, Duke University, Durham, United States of America., Walsh KM; Department of Neurosurgery, Duke University, Durham, United States of America.
Jazyk:	angličtina
Zdroj:	The Journal of clinical investigation [J Clin Invest] 2024 Nov 12. Date of Electronic Publication: 2024 Nov 12.
DOI:	10.1172/JCI181342
Abstrakt:	Human cytomegalovirus (HCMV) profoundly impacts host T and natural killer (NK) cells across the lifespan, yet how this common congenital infection modulates developing fetal immune cell compartments remains underexplored. Using cord blood from neonates with and without congenital HCMV (cCMV) infection, we identify an expansion of Fcγ receptor III (FcγRIII)-expressing CD8+ T cells following HCMV exposure in utero. Most FcγRIII+ CD8+ T cells express the canonical αβ T cell receptor (TCR) but a proportion express non-canonical γδ TCR. FcγRIII+ CD8+ T cells are highly differentiated and have increased expression of NK cell markers and cytolytic molecules. Transcriptional analysis reveals FcγRIII+ CD8+ T cells upregulate T-bet and downregulate BCL11B, known transcription factors that govern T/NK cell fate. We show that FcγRIII+ CD8+ T cells mediate antibody-dependent IFNγ production and degranulation against IgG-opsonized target cells, similar to NK cell antibody-dependent cellular cytotoxicity (ADCC). FcγRIII+ CD8+ T cell Fc effector functions were further enhanced by interleukin-15 (IL-15), as has been observed in neonatal NK cells. Our study reveals that FcγRIII+ CD8+ T cells elicited in utero by HCMV infection can execute Fc-mediated effector functions bridging cellular and humoral immunity and may be a promising target for antibody-based therapeutics and vaccination in early life.
Databáze:	MEDLINE
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