CMV-reactive Vdelta1 gd T cells are equally cytotoxic to CMV-specific ab T cells in HLA-A*02 healthy donors
| Authors | |
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| Year of publication | 2022 |
| Type | Conference abstract |
| MU Faculty or unit | |
| Citation | |
| Description | Cytomegalovirus (CMV) infection is responsible for significant morbidity and mortality in immunocompromised patients, namely haematopoietic cell transplant recipients (HCT) despite prophylaxis and pre-emptive treatment. Earlier, we demonstrated the role of Vdelta1 gamma-delta (gd) T cells in the reconstitution of CMV immunity post-transplant. Here, we analysed CMV+ healthy donors with five most commonly presented alleles including HLA-A*02 (n=23), HLA-A*01 (n=17), HLA-A*24 (n=10), HLA-B*07 (n=5) and HLA-B*35 (n=10) for frequencies and phenotypes of Vd1+ gd T cells and CMV-specific alpha-beta (ab) T cells in the same donors. Multicolour flow cytometry was used to directly compare Vd1 gd T cells with donor paired CMV-specific ab T cells that have been identified by CMV-specific MHC Pentamers (ProImmune Limited, UK) for HLA-A*0201 (NLV), HLA-A*0101 (YSE), HLA-A*2402 (VYA), HLA-B*0702 (TPR) and HLA-B*3501 (IPS) alleles. Second, we determined the cytotoxic reactivity of ab and gd T cells against CMV-infected MRC-5 fibroblasts in HLA-A*02 donors in 4h flow cytometric killing assays. Both, ab CMV-specific T cells and pair-matched freshly isolated or ex-vivo cultured Vd1 gd T cells were highly lytic to CMV-infected targets at 10:1 E:T ratio with no significant differences in specific lysis observed between the ab and gd T cells (p>0.05). Next, we compared the microRNA (miRNA) expression profiles for Vd1 gd T cells and ab T cells isolated from the same HLA-A*02 and HLA-A*01 donors. We identified 20 miRNAs differentially expressed (P<0.001) for HLA-A*02 and 10 miRNAs for HLA-A*01 allele (P<0.05) known to be associated with suppression of tumour cell proliferation, invasion and metastasis in addition to regulating inflammation in multiple cancers predicting patient prognosis and disease outcome. In summary, we provide further evidence for CMV reactive Vd1 gd T cells implicated in CMV chronic infection that could be used in adoptive transfer in HCT recipients regardless of HLA status. |
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