Numerical and functional alterations of circulating gammadelta T lymphocytes in aged people and centenarians.

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.

Reduced number and impaired function of circulating gamma delta T cells in patients with cutaneous primary melanoma.

We studied the peripheral representation, in vitro expansion, cytokine production, and cytotoxicity of gamma delta T lymphocytes from 23 patients with cutaneous primary melanoma and 28 healthy subjects. We demonstrated that the absolute number and the percentage of circulating gamma delta + T cells were significantly reduced in melanoma patients in comparison with healthy subjects. The decrease was due to a reduction of V delta 2 T cells, whereas the number of V delta 1 T cells was not affected. As a consequence, the V delta 2/V delta 1 ratio was inverted in melanoma patients. A lower percentage of gamma delta + T cells producing tumor necrosis factor-alpha or interferon-gamma was found in melanoma patients. After a 10 d in vitro culture, both the percentage and the expansion index of gamma delta T cells, and in particular of V delta 2 subset, were significantly reduced in melanoma patients in comparison with healthy subjects. The cytotoxicity of sorted gamma delta T cells against tumor cell lines and the percentage of gamma delta T cells producing perforins were preserved in melanoma patients. The numerical and functional impairment of gamma delta T cells could contribute to the inadequate immune response found in melanoma patients and offers the potentiality for the planning of new approaches of immune therapy of malignant melanoma.