ROLE OF CYTOMEGALOVIRUS SEROPOSITIVITY ON AGEING OF THE INNATE IMMUNE SYSTEM OF GAMMA-DELTA T CELLS IN HEALTHY DONORS

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Authors

KNIGHT Andrea PISKACEK Martin VŠIANSKÁ Pavla PACASOVÁ Rita VAŠKŮ Anna

Year of publication 2014
Type Appeared in Conference without Proceedings
MU Faculty or unit

Faculty of Medicine

Citation
Description Both innate and adaptive immunity are affected by immunosenescence. A number of age-associated alterations in T cell immunity is strongly affected by infection with the persistent beta-herpesvirus HHV5 (cytomegalovirus, CMV). CMV-specific alpha-beta T cells are the principal effector T cells in CMV infections in normal immunocompetent individuals. However, the role of innate effector Vdelta1 and Vdelta2 gamma-delta T cell populations in anti-CMV responses parallel to CMV-specific alpha-beta T cells in the same HLA-A*02, HLA-A*01, HLA-A*24, HLA-A*07, and HLA-A*35 donors is not currently fully understood. The mechanisms accounting for changes in the T cell repertoire, and biomarkers of ageing are currently the subject of intensive research. We have previously shown that Vdelta1 gamma-delta T lymphocytes are expanded in CMV seropositive healthy donors compared to CMV seronegative individuals (p=0.0002) suggesting their direct involvement in anti-CMV immune responses. Interestingly, levels of Vdelta2 gamma-delta T lymphocytes show no difference between the CMV groups but dramatically reduce with increasing age in contrast to Vdelta1 gamma-delta T cells that remain similar during ageing. More importantly Vdelta1 gamma-delta T lymphocytes isolated and expanded from CMV seropositive volunteers exert specific cytotoxicity against CMV-infected MRC5 fibroblasts (Knight et al., Blood 2012). We also reported comparable anti-CMV specific cytotoxicity elicited by Vdelta1 gamma-delta T lymphocytes isolated from CMV seronegative donors. We have used fresh whole peripheral blood samples from CMV+ donors (n=27; age 31-62 years; median 47) and CMV- (n=16; 30-60 years; median 35.5) to determine the frequencies of Vdelta1, Vdelta2 gamma-delta T cells and CMV-specific alpha-beta T cells by multicolour flow cytometry. In CMV+ donors, the median levels of Vdelta1 and Vdelta2 cells were 3.75 (range 0.4-7.5%) and 5.43 (0.6-10.4%) of CD3+ T cells respectively. In contrast, the frequencies of CMV-specific alpha-beta T cells in the same HLA-A*02 donors were 0.55 (0.3-4.4%), other HLA alleles were numerically comparable to HLA-A*02 allele. We also compared the cytotoxic reactivity between the effector T cell populations against CMV-infected MRC5 fibroblasts. Importantly, we show an equal cytotoxic reactivity of CMV-specific alpha-beta T cells and Vdelta1 gamma-delta T lymphocytes. Our results suggest that CMV-reactive Vdelta1 gamma-delta T cells represent a novel approach for future adoptive immunotherapy in a HLA-independent manner.
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