INCREASED SUSCEPTIBILITY OF TUMORIGENICITY AND DECREASED ANTI-TUMOR EFFECT OF DC VACCINATION IN AGED MICE ARE POTENTIALLY ASSOCIATED WITH INCREASED NUMBER OF NK1.1+CD3+ NKT CELLS
1Research Unit, Saskatchewan Cancer Agency, Department of Oncology, University of Saskatchewan, Saskatoon S7N 4H4, Canada 2Research Unit, Saskatchewan Cancer Agency, Department of Geography, University of Saskatchewan, Saskatoon S7N 4H4, Canada
Abstract. Aim: It is established that aging leads to declines in immune function. However, the mechanisms underlying remain poorly understood. Methods: In this study, we compared the tumoriginecity of MO4 (ovalbumin-transfected) tumor cells, the efficacy of dendritic cell (DC) vaccination and cytotoxic T lymphocytes (CTLs), and the number of NK1.1+CD3+ NKT cells between aged mice and young mice using T cell proliferation and cytotoxicity assays and flow cytometry. Results: We showed that, in comparison to young mice, aged mice are 10-fold more susceptible to tumorigenicity of MO4 tumor cells. Aged mice immunized with bone marrow-derived DCs pulsed with ovalbumin (DCOVA) survived significantly shorter after challenge with MO4 tumor cells as compared to equally treated young mice. Furthermore, CTLs from aged mice immunized with DCOVA displayed 4-fold weaker cytotoxicity as compared to CTLs from immunized young mice. Interestingly, the number of NK1.1+CD3+ NKT cell significantly increase with aging (p < 0.05). Of particular importance, NK1.1+CD3+ NKT cells isolated from aged mice suppress the proliferation of T cells. Conclusions: Based on these data, we conclude that NK1.1+CD3+ NKT cells from aged mice mediate immunosuppression, and further suggest that increased number of NK1.1+CD3+ NKT cells in aged mice might, among others, diminish their immune function by mediation of immunosuppression.
