*PURPOSE: Cytomegalovirus (CMV) infection elicits rapid and sustained expansion of circulating T cells. We aim to explore the unusual, heterogenous subsets of CD8 T cells that exhibit receptors commonly found on natural killer (NK) cells, and characterize their association with CMV and their longitudinal persistence in kidney transplant recipients (KTRs).
*METHODS: We collected PBMCs from KTRs longitudinally, including Baseline (approximately 3mo-post Tx), 1-week post-CMV viremia, 1-year and 2-years post-Tx. We performed single-cell RNA sequencing on purified CD8 T cells from 4 CMV PCR+ patients, including 2 CMV seropositive (S/P) and 2 seronegative (S/N), and their CMV PCR- controls. We evaluated peripheral blood CD8 T cell response of KTRs with CMV primary infection (n=4) and reactivation (n=4), with paired CMV- KTRs
*RESULTS: We identified T cells expressing transcripts of receptors commonly found on natural killer (NK) cells, including Fcγ receptors (CD16) accumulate in the CD8 T cell pool of CMV seropositive (S/P) patients and seronegative (S/N) KTRs after viremia. Among the 22 clusters defined by single-cell RNA sequencing, there were four highly differentiated FCGR3A (CD16)+ clusters (0, 10, 13 and 14) with high cytotoxicity potential (GZMs, GNLY, PFR1+) (FIG 1A-B). We found that FCGR3A is highly induced longitudinally in S/P KTRs, suggesting their association with CMV viremia (FIG 1C). Despite expressing FCGR3A, these four clusters have differentially expressed genes including NK receptors (NKR), transcription factors, and functional markers. S/N KTRs with primary CMV infection had impaired establishment and maintenance of T cell memory response long-term post-Tx. Patients with repeated viremia displayed an increased CD8 T cell response to anti-CD16 stimulation. In contrast, S/P KTRs control latent CMV infection under immunosuppression, but the presence of CMV-induced CD16+ CD8 T cells suggests an NK-like potential to mediate allograft injury, via ADCC in KTRs producing donor-specific anti-HLA antibodies. [

]CITATION INFORMATION: Sun A., Pickering H., Sen S., Parmar R., Reed E. Molecular Mapping of Nk Like Cd8 T Cell Atlas in Kidney Transplantation AJT, Volume 23, Issue 6, Supplement 1.

Angela (Yumeng) Sun B.S.

University of California Los Angeles

Appearances