Age-associated alteration of γδ T-cell repertoire and different profiles of activation-induced death of Vδ1 and Vδ2 T cells

Abstract

It has been suggested that γδ T cells are involved in certain autoimmune disorders. To establish reference data for clinical studies to explore the role of γδ T cells in autoimmune bone marrow failure syndrome, we examined the γδ T-cell repertoire in 120 healthy Japanese individuals by flow cytometry. The average numbers of T lymphocytes in blood were as follows: 1,084 ± 369 (SD) αβ T cells, 68 ± 44 γδ T cells, 16 ± 12 Vδ1 T cells, and 43 ± 36 Vδ2 T cells (/μl). Absolute numbers of γδ T cells decreased with aging (R = -0.378, P < 0.001). The decrease of γδ T cells was the result of reduction of Vδ2, but not of Vδ1, T cells. Numbers of Vδ2 T cells were significantly higher in male than in female donors (P = 0.007). The Vδ2 T cells but not Vδ1 T cells showed a rapid reduction in cell numbers on mitogen stimulation, which was accompanied by modest down-regulation of Bcl-2 protein expression. These results indicate that age and gender have a major impact on γδ T-cell repertoire in Japanese donors, as well as European and American donors. The age-related decrease of Vδ2 T cells may be explained by their susceptibility to activation-induced cell death.

Differential Impact of Age and Cytomegalovirus Infection on the γδ T Cell Compartment

“…We show that both aging and CMV infection impact independently on the gd T cell compartment. This dual effect provides an explanation for the discrepancy in the changes observed between Vd2 2 and Vd2 + gd T cells in elderly (10,11). Although the frequency of Vd2 + gd T cells The analysis of global gd T cell frequency and phenotype suggests that gd and ab T cell pools experience similar changes with advanced age, characterized by a decreased absolute number and a bias toward CD27 2 CD45RA + cells.…”

“…They can respond to a number of stimuli (i.e., recognized by their TCR, NK-like receptors, as well as TLRs) and engage potent effector functions both in terms of cytokine and chemokine production capacity (e.g., IFN-g, IL-17, and RANTES) and direct cytotoxicity (9). In the elderly, both the absolute numbers and percentages of total gd T lymphocytes have been shown to decrease (10,11). Interestingly though, subsets of gd T cells appear to be differentially affected.…”

“…Interestingly though, subsets of gd T cells appear to be differentially affected. The numbers of Vd2 + cells, which is the predominant population of circulating gd T cells, decrease with age, in contrast to Vd1 + cells that remain stable (10,11). The factors involved in the differential regulation of gd T cells with aging are unclear.…”

Defining the nature of human γδ T cells: a biographical sketch of the highly empathetic

“…[113][114][115] The life events that affect cd T cell function are not limited to infectious and physiological insults, but also include psychological stress that especially mobilize terminally differentiated 'effector memory' cells characterized as being negative for cell surface marker CD27 but expressing CD45RA. 116 This phenotype represents cd T cells that have already tackled some hurdles in their life and have reduced proliferative capacity, but are still able to pull the trigger given their highly cytolytic potential.…”

“…116 This phenotype represents cd T cells that have already tackled some hurdles in their life and have reduced proliferative capacity, but are still able to pull the trigger given their highly cytolytic potential. 117 Thus, differences in cd T cell numbers in relation to parameters such as gender and race that are inconsistent across the various populations studied 89,[113][114][115] may partly reflect the discrepant burdens that contribute to overall life stress experienced by members of these groups. For example, African Americans in Baltimore were found to have significantly lower peripheral blood cd T cells in comparison to their Caucasian counterparts; 113 however, Africans from Ghana have significantly more cd T cells (of both the Vd1 and Vd2 T cell variety) in comparison to Europeans.…”