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Human cytomegalovirus expands a CD8 + T cell population with loss of BCL11B expression and gain of NK cell identity.
- Source :
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Science immunology [Sci Immunol] 2021 Sep 24; Vol. 6 (63), pp. eabe6968. Date of Electronic Publication: 2021 Sep 24. - Publication Year :
- 2021
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Abstract
- CD8 <superscript>+</superscript> 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 <superscript>+</superscript> TCRαβ <superscript>+</superscript> CD8 <superscript>+</superscript> T cells are associated with prior human cytomegalovirus (HCMV) exposure. In addition to expressing several NK cell markers such as CD56 and KIR, NKG2C <superscript>+</superscript> CD8 <superscript>+</superscript> T cells are oligoclonal and do not up-regulate PD-1 even in response to persistent activation. Furthermore, we found that NKG2C <superscript>+</superscript> CD8 <superscript>+</superscript> 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 <superscript>+</superscript> CD8 <superscript>+</superscript> T cells when compared with conventional NKG2C <superscript>−</superscript> CD8 <superscript>+</superscript> T cells. BCL11B deletion in conventional CD8 <superscript>+</superscript> T cells resulted in the emergence of a similar innate-like CD56 <superscript>+</superscript> CD94 <superscript>+</superscript> DAP12 <superscript>+</superscript> NKG2C <superscript>+</superscript> CD45RA <superscript>+</superscript> CCR7 <superscript>−</superscript> PD-1 <superscript>−/low</superscript> T cell population with activity against HLA-E <superscript>+</superscript> targets. On the basis of their intrinsic capacity to recognize diseased cells coupled with lack of PD-1 induction, NKG2C <superscript>+</superscript> CD8 <superscript>+</superscript> 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.
Details
- Language :
- English
- ISSN :
- 2470-9468
- Volume :
- 6
- Issue :
- 63
- Database :
- MEDLINE
- Journal :
- Science immunology
- Publication Type :
- Academic Journal
- Accession number :
- 34559552
- Full Text :
- https://doi.org/10.1126/sciimmunol.abe6968