Regulation Of Aged T Cell Function By CD137 And CD28

Objective: To discuss the characteristic alteration of aged T cell function and its regulation mechanism, we compared the changes of T cells in D-galactose induced subacute senile mice and aged mice and observed the effects of CD 137 and CD28 on the proliferation, IL-2 secretion, cell survival, expression of bcl-2 and telomerase activity of T cells in D-galactose induced subacute senile mice and aged mice.Methods: Subacute senile mice model was established by injection of D-galactose. The spleen T cells of D-galactose induced subacute senile group (D-gal model group for short), aged group, control group and young group were isolated and stimulated in vitro with conA + IgG or conA + CD137mAb or conA + CD28mAb.The proliferation of T cells was assay by CCK-8, the apoptotic rate was detected by flow cytometry and IL-2 concentrations in cell culture supernate were determined by ELISA. The expression of bcl-2 of T cells in D-gal model group and aged group was detected by RT-PCR and FCM. Telomerase activity was determined by TRAP ELISA.Results: (1) Compared with young group and control group, cell proliferation, IL-2 secretion and cell survival of T cells in D-gal model group and aged group are significantly decreased. (2) conA + CD137mAb and conA + CD28mAb can significantly promote cell proliferation, IL-2 secretion and cell survival of T cells in D-gal model group and aged group. CD 137 mAb had less effect on both group than CD28 mAb. But in the same activating condition, the activation of T cells in D-gal model group and aged group was significantly lower than T cells in control and young group. (3) conA + CD137mAb and conA + CD28mAb can promote the expression of bcl-2 protein and bcl-2 mRNA of T cells in D-gal model group and aged group. CD28 mAb had greater effect on both group than CD137 mAb. (4) Compared with young group and control group, telomerase activity of T cells in D-gal model group and aged group is significantly decreased. ConA + CD137mAband conA + CD28mAb can promote telomerase activity of T cells in D-gal model group and aged group. But in the same activating condition, telomerase activity of T cells in D-gal model group and aged group was significantly lower than T cells in control and young group.Conclusions: (1) There is a significant decrease in cell proliferation, IL-2 secretion and an increase in cell apoptotic rate in activated T cells in aged group and D-gal model group induced for 5 months, which are the main age-associated alterations in T cells function. (2) CD 137 can transfer costimulatory signal independently to enhance cell proliferation, IL-2 secretion and cell survival in activated T cells in aged group and D-gal model group. But compared with the most important costimulatory molecular CD28, CD 137 has less effect on T cell activation. (3) CD 137 and CD28 can increase the expression of bcl-2 of activated T cells in aged group and D-gal model group. Bcl-2 maybe the basic molecular through which costimulatory molecular can decrease activated T cell apoptosis. CD 137 has less effect on bcl-2 expression than CD28. (4) Compared with young group and control group, telomerase activity of T cells in D-gal model group and aged group is significantly decreased. CD 137 and CD28 can promote telomerase activity of T cells in D-gal model group and aged group. As being costimulatory moleculars, they can also promote telomerase activity of T cells in control group and young group. The result indicates that CD 137 and CD28 are important moleculars that regulate aged T cell function. (5) CD 137 and CD28 can transfer costimulatory signal to promote cell activation, bcl-2 expression and telomerase activity, but neither of them can promote aged T cell function to the level of young T cell. It indicates that T cell senescence is a complicated integrative alteration and age-associated defects in signal transfer has great impact on the function of aged T cell. (6) CD 137 has less effect on promoting cell proliferation, IL-2 secretion, cell survival, bcl-2 expression and telomerase activity than CD28. It indicates that as the most widely expressed costimulatory molecular, CD28 is very important in regulating aged T cell function. As CD 137 can transfer costimulatory signal independently to promote T cell activation, it may play an important role in retaining the function of aged T cell. CD 137 is an important costimulatory molecular that regulates function of aged T cell.