The late effects of selected immunosuppressants on immunocompetence, disease incidence, and mean life-span II. Cell-mediated immune activity

Abstract

The late effects of various immunosuppressive insults on cell-mediated immunity in mice were studied in an attempt to assess the role of immune surveillance in the aging process. Results were obtained using susceptibility to allogeneic tumor cell challenge, graft-versus-host reaction (GVHR), blastogenic response to PHA, a thymus derived T cell-specific plant mitogen, and cytolytic activity against allogeneic tumor cells as measures of immunologic activity. In vivo studies late in life show that resistance to allogeneic tumor cells is significantly decreased in thymectomized mice, whereas those treated with cortisone, cyclophosphamide and sublethal X-ray remain unchanged. Spleen cells from only the thymectomized and the sublethally irradiated mice show reduced activity in the GVHR. No difference is seen in the activity of bone marrow cells. Results consistent with these findings were obtained in in vitro studies. Thus spleen cells from thymectomized or sublethally irradiated mice show decreased activity is response to PHA, whereas no change is seen in spleen cells from other treated groups. Hence, surgical and physical insults are more likely to induce long-lasting immunosuppression in those immunocompetent tissues whose activity normally diminishes with advancing age. Furthermore, the degree of immunosuppression seen in this study is not of the order of magnitude that one could reasonably predict a significant decrease in mean life-span.

Immunity, Age and Loss of Immunohomeostasis1

“…Alteration in regulatory T cells may be responsible for some of these immunologic abnormalities, since removal of the thymus increases their occurrence in young mice [ Cell-mediated immunity also decreases, as demonstrated by the response of mouse spleen cells to phytohemagglutin (PHA) ( Figure 6). Other cell-mediated immune responses showing similar age-related alterations include delayed type hypersensitivity skin reactions [Crowle et al, 1981], resistance to challenge with intracellular pathogens [Gardner & Remington, 1977], resistance to challenge with tumor cells [Thompson, 1976], primary skin allograft rejection [Menon et al, 1974], graft-versus-host reaction [Peterson et al, 1975], cytolytic T cell responses [Menon et al, 1974], mixed lymphocyte reactions [Kishimoto et al, 1978], T helper cell activity [Price & Makinodan, 1972], T cell growth factor production [Chang et al, 1982], and T suppressor cell activity [Barthold et al, 1974]. Variability of age influence on cell-mediated immunity has been reported in a few studies, and the most inconsistent involves the suppressor T cells.…”