In:
Science Immunology, American Association for the Advancement of Science (AAAS), Vol. 6, No. 63 ( 2021-09-24)
Abstract:
CD8 + T cells not only are critical mediators of adaptive immunity but also may exhibit innate-like properties such as surface expression of NKG2C, an activating receptor typically associated with natural killer (NK) cells. We demonstrate that, similar to NK cells, NKG2C + TCRαβ + CD8 + T cells are associated with prior human cytomegalovirus (HCMV) exposure. In addition to expressing several NK cell markers such as CD56 and KIR, NKG2C + CD8 + T cells are oligoclonal and do not up-regulate PD-1 even in response to persistent activation. Furthermore, we found that NKG2C + CD8 + T cells from some individuals exhibited strong effector function against leukemia cells and HCMV-infected fibroblasts, which was dictated by both NKG2C and TCR specificity. Transcriptomic analysis revealed that the transcription factor BCL11B , a regulator of T cell developmental fate, is down-regulated in NKG2C + CD8 + T cells when compared with conventional NKG2C − CD8 + T cells. BCL11B deletion in conventional CD8 + T cells resulted in the emergence of a similar innate-like CD56 + CD94 + DAP12 + NKG2C + CD45RA + CCR7 − PD-1 −/low T cell population with activity against HLA-E + targets. On the basis of their intrinsic capacity to recognize diseased cells coupled with lack of PD-1 induction, NKG2C + CD8 + T cells represent a lymphocyte population that resides at the boundary between innate and adaptive immunity, presenting an attractive alternative for cellular therapy, including CAR T cell–based therapies.
Type of Medium:
Online Resource
ISSN:
2470-9468
DOI:
10.1126/sciimmunol.abe6968
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2021
