Abstract: Influenza is an important cause of morbidity and mortality in the elderly and influenza vaccination has shown a decreased efficacy in aged people. Both gammadelta- and alphabeta-T cell responses, which are believed to play an important role in controlling influenza infection, are impaired during aging. The aim of this study was to evaluate the ability of influenza vaccine to induce cellular immune responses mediated by gammadelta- and alphabeta-T cells in healthy elderly subjects. After influenza vaccination, an increased proportion of Vgamma9Vdelta2 T cells having reduced proliferative capacity and increased perforin production, and then a differentiated effector/memory phenotype, was present. The peripheral number and the cytokine production of gammadelta T cells were not changed. A significant decrease of CD4 and CD8 naïve T cells and a corresponding increase of CD4 and CD8 memory T cells were found. The in vitro stimulation of PBMCs from elderly subjects with influenza antigens increased their proliferative capacity and the production of both IFNgamma and IL-4. The vaccine was clinically effective, since in the outbreak period, only one influenza case was noted. The results reported in this study demonstrate the activation of both gammadelta- and alphabeta-T cell responses in healthy elderly after influenza vaccination.

Abstract: We recently demonstrated that numerical and functional alterations of gammadelta T cells are present in healthy elderly. Here we observed that the decreased absolute number of Vgamma9Vdelta2 T cells present in old subjects in comparison with young/adult and middle aged donors is due to the reduction of naive and central memory Vgamma9Vdelta2 T cells bearing CD27 and CCR7 antigens. The proportion of effector/memory Vgamma9Vdelta2 T cells lacking CD27 or CCR7 markers was significantly increased in the peripheral blood of old subjects in comparison with younger donors. Moreover, the percentage of CD69+ gammadelta T cells was significantly increased in old subjects in comparison with younger donors after overnight activation, confirming that more effector cells are available in aged people. A functional analysis in young/adult and middle aged donors revealed that effector/memory CD27- Vgamma9Vdelta2 T cells are increased after 10-days of in vitro colture in the presence of isopentenylpyrophosphate (IPP) and IL-2. In contrast, the IPP+IL-2 mediated differentiation and expansion of CD27- effector/memory cells was absent in old subjects, confirming a lack of naive and central memory cells responding to IL-2. Accordingly, the expansion index of effector/memory CD27- Vgamma9Vdelta2 T cells was negatively correlated with the donor age. Finally, terminally differentiated Vgamma9Vdelta2 T cells measured as perforin content after 10-day in vitro expansion showed no age-related difference. These data demonstrated a shift of the circulating gammadelta T cell population towards CD27- and CCR7- effector T cells in the elderly with the reduction of immature CD27+ and CCR7+ T cell precursors.

Abstract: BACKGROUND: In a previous study we demonstrated the existence of numerical and functional alterations of gammadelta T cells in healthy elderly. Recently, we analysed the involvement of gammadelta T lymphocytes in malignant melanoma, describing a lower frequency of circulating gammadelta T cells, an altered pattern of cytokine production, and an impaired in vitro expansion of these cells in primary cutaneous melanoma patients. METHODS: In this study we investigated the existence of numerical and functional alterations of circulating gammadelta T cells in young/adult and old melanoma patients, comparing the data obtained with age-matched healthy subjects. RESULTS: We demonstrated that the number of circulating gammadelta+ T cells was significantly and similarly reduced in young/adult and old melanoma patients and in old healthy subjects in comparison with young healthy donors. The decrease was due to a reduction of Vdelta2 T cells whereas the number of Vdelta1 T cells was not affected. A higher percentage of gammadelta+ T cells producing TNF-alpha was found in old healthy donors, whereas a reduced number of TNF-alpha-producing gammadelta+ T cells was present in melanoma patients independently by age. No significant difference was observed in IFN-gamma production. After a 10-day in vitro culture, both the percentage and the expansion index of gammadelta T cells, and in particular of Vdelta2 subset, were significantly and similarly reduced both in young/adult and old melanoma patients, and in healthy aged people, in comparison with young/adult healthy subjects. CONCLUSIONS: Our study demonstrates that the numerical and functional impairment of gammadelta T cells found in melanoma patients is not correlated with age and that it has characteristics very similar to the alterations of gammadelta T cells found in old healthy subjects. We suggest that a similar impairment of gammadelta T cell population may be related to the increased susceptibility to tumors present in the elderly as well as in the pathogenesis of malignant melanoma.

Abstract: The aim of this study was to evaluate the peripheral representation, in vitro expansion, cytokine production, and cytotoxicity of gammadelta T lymphocytes from 104 healthy subjects ranging in age from 19 to 103 years. We demonstrated that the absolute number of circulating gammadelta(+) T cells was reduced significantly in old people and centenarians in comparison with young subjects as a consequence of the age-related decreased lymphocyte number. The decrease was a result of an age-dependent reduction of Vdelta2 T cells, whereas the absolute number of Vdelta1 T cells was unaffected by age. As a consequence, the Vdelta2/Vdelta1 ratio was inverted in old subjects and centenarians. A higher percentage of gammadelta(+) T cells producing tumor necrosis factor alpha was found in old donors and centenarians, whereas no age-related difference was observed in interferon -gamma production. After a 10-day in vitro expansion, a twofold lower expansion index of gammadelta T cells, and particularly of a Vdelta2, but not of a Vdelta1 subset, was found in old people and centenarians in comparison with young subjects. The cytotoxicity of sorted gammadelta T cells was preserved in old people and centenarians. The alteration of gammadelta T cells could contribute to the age-related derangement of T cell-mediated, adoptive responses and may represent a new characteristic of immunosenescence.