Cytolytic activity of mitogen activated old and young mouse spleen cells against tumor target cells expressing high or low levels of Fas antigen.

Rajiv K Saxena,William H Adler

doi:10.1038/emm.1999.23

Abstract

Sensitivity of Fas expressing tumor cells (high levels in Hut78 & Jurkat; low levels in P815) toward the cytotoxic Con-A (5 microg/ml) activated spleen cells from young (12 to 16 week old males) and old (2 year old males) mice were studied. The spleen cells from young mice activated for a day showed high levels of cytotoxic activity against Hut78 and Jurkat cell lines but not against P815 cells. The cytotoxic activity against P815 cells were detected in the spleen cells from old but not young mice following a longer period of Con-A activation (three days). Comparable levels of cytotoxic activity against Hut78 and Jurkat cells were observed in the spleen cells from both young and old mice following three days of activation. Treatment of Hut78 cells with anti-Fas antibody affected the tumor cells become resistant against the cytotoxic activity of the spleen cells from young mice in a dose dependent manner however P815 cells were not affect by the anti-Fas antibody treatment. These results show that there are differences in the sensitivity of target tumor cells toward Con-A induced cytotoxic spleen cells from young and old mouse. Mitogen-induced cytotoxic lymphocytes from young mouse spleen appear to kill targets through mechanisms involving Fas antigen, specially, in early stage (1 day) of activation. Old mouse spleen cells generated high levels of cytotoxic cells in later phase (3 days), which appear to kill through Fas-unrelated mechanisms.

Highlights

Many parameters of T-cell activity decline with age
While most T-cell functional activity appears to decline with age, we found that mitogen (Con-A) stimulated spleen cells from old mice compared to young mice, generated markedly higher levels of cytotoxic activity against several tumor cell lines like YAC, P815 and EL4 (Saxena et al, 1988a)
Levels of Fas expression on Hut78, Jurkat and P815 tumor cell lines Fas-Fas ligand (FasL) interaction has been recognized as an important killing signal for Fas expressing tumor target cells

Summary

Introduction

Many parameters of T-cell activity decline with age. These include T-cell proliferation in response to stimulation through T cell receptor and co-stimulators (Engwerda et al, 1994; Lerner et al, 1988; Song et al, 1993), production and response to growth promoting cytokines (Ernst et al, 1993; Nagelkerken et al, 1991; Saxena et al, 1988) and generation of cytotoxic T-cells (Hirano and Nordin, 1976; Powers and Belshe, 1993; Mbawuike et al, 1997). We have re-investigated the issue of mitogen induced cytotoxic cells in old and young mouse spleen cells, in order to assess whether the differences in the cytotoxic cell response obtained in the two cases may arise due to differential activation of effector cells resulting in different killing mechanisms. For this purpose, cytotoxic activity of lectin activated spleen cells from young and old mouse spleen cells was studied by using targets which express high or low levels of Fas. The P815 cell line expresses low levels of Fas antigen and is not susceptible to lysis through Fas-FasL mechanism (Tsutsui 1996), whereas the Jurkat and Hut cell lines express high levels of Fas antigen and are susceptible to FasL mediated lysis (Alderson et al, 1994; Wong and Goeddel, 1994).

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