Abstract
BackgroundIn a previous study we demonstrated the existence of numerical and functional alterations of γδ T cells in healthy elderly. Recently, we analysed the involvement of γδ T lymphocytes in malignant melanoma, describing a lower frequency of circulating γδ T cells, an altered pattern of cytokine production, and an impaired in vitro expansion of these cells in primary cutaneous melanoma patients.MethodsIn this study we investigated the existence of numerical and functional alterations of circulating γδ T cells in young/adult and old melanoma patients, comparing the data obtained with age-matched healthy subjects.ResultsWe demonstrated that the number of circulating γδ+ 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 Vδ2 T cells whereas the number of Vδ1 T cells was not affected. A higher percentage of γδ+ T cells producing TNF-α was found in old healthy donors, whereas a reduced number of TNF-α-producing γδ+ T cells was present in melanoma patients independently by age. No significant difference was observed in IFN-γ production. After a 10-day in vitro culture, both the percentage and the expansion index of γδ T cells, and in particular of Vδ2 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.ConclusionsOur study demonstrates that the numerical and functional impairment of γδ T cells found in melanoma patients is not correlated with age and that it has characteristics very similar to the alterations of γδ T cells found in old healthy subjects. We suggest that a similar impairment of γδ 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.
Highlights
T lymphocytes bearing the γδ T cell receptor (TCR) represent a minor population of human peripheral lymphocytes (1–10%), the majority of them expressing the CD3+CD4-CD8- phenotype [1,2,3,4]
Peripheral blood lymphocytes from 9 young/adult and 12 old melanoma patients and 10 young and 13 old healthy subjects were analysed for the percentage and the absolute number of γδ T cells through double staining with antiCD3 and anti-γδ monoclonal antibodies (mAbs)
The Vδ2 and Vδ1 subsets were differently represented in the four groups: in young/adult healthy controls the Vδ2 subset was predominant (Vδ2/Vδ1 ratio = 2.2) whereas in old healthy donors and in young/adult and old melanoma patients the Vδ2/Vδ1 ratio was progressively decreased
Summary
T lymphocytes bearing the γδ T cell receptor (TCR) represent a minor population of human peripheral lymphocytes (1–10%), the majority of them expressing the CD3+CD4-CD8- phenotype [1,2,3,4]. In our previous paper [11], we have evaluated the role of γδ T cells from young, old, and centenarian subjects, demonstrating an age-dependent alteration of γδ T lymphocytes, with a lower frequency of circulating γδ T cells, an altered pattern of cytokine production, and an impaired in vitro expansion of these cells. We described an impairment of γδ T cell population in patients with cutaneous primary melanomas, with a decrease of their absolute number and percentage, an altered cytokine production, and a reduced expansion of γδ T cells, and of the Vδ2 subset [14]. We analysed the involvement of γδ T lymphocytes in malignant melanoma, describing a lower frequency of circulating γδ T cells, an altered pattern of cytokine production, and an impaired in vitro expansion of these cells in primary cutaneous melanoma patients
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