ROLE OF CYTOMEGALOVIRUS SEROPOSITIVITY ON AGEING OF THE INNATE IMMUNE SYSTEM OF GAMMA-DELTA T CELLS IN HEALTHY DONORS
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| Year of publication | 2014 |
| Type | Appeared in Conference without Proceedings |
| MU Faculty or unit | |
| 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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