Selective induction and inhibition of direct and lectin-dependent cell-mediated cytotoxic reactivity
Date of Original Version
The immune reactivity of mice (C57BL/6, H-2b) which had been challenged with various numbers (102-108) of allogeneic tumor cells (P815, H-2d) was assessed at various times after challenge. Challenge with a high dose (108) of tumor cells resulted in the development of direct cytotoxicity (DCMC), lectin-dependent cytotoxicity (LDCC), delayed-type hypersensitivity (DTH), and antibody production, whereas challenge with lower doses (< 106) of tumor cells favored development of DTH and LDCC with marginal or no DCMC or antibody production. Spleen cells from low-dose alloimmune animals failed to produce DCMC when cultured with P815 cells in vitro and were capable of nonspecifically suppressing the DCMC response of normal spleen cells in MLC. Treatment with cyclophosphamide (100 mg/kg) prior to alloimmunization did not alter the pattern of DTH and cytotoxic reactivity, although treatment after alloimmunization was immunosuppressive for all forms of reactivity. When low-dose challenge was followed by cyclophosphamide treatment and a subsequent high-dose challenge, selective inhibition of DTH, LDCC, and suppressor activity, but not DCMC, was observed. The data suggest that (a) the initial challenge dose plays a significant role in determining which effector and regulatory populations will be activated and what direction the expression of immune reactivity will take; (b) the activated responding populations of DTH, DCMC, and LDCC effector cells are sensitive to cyclophosphamide treatment, whereas the precursors of each are resistant to the effects of the drug; (c) low-dose alloimmunization may be used in combination with cyclophosphamide treatment to modulate DTH, DCMC, and LDCC reactivity in a selective manner; (d) the cytotoxic effector cells responding to highdose challenge and mediating DCMC and those responding to low-dose challenge and mediating LDCC appear to arise from distinct precursor populations. © 1981.
Publication Title, e.g., Journal
Parker, B. M., and D. C. Laux. "Selective induction and inhibition of direct and lectin-dependent cell-mediated cytotoxic reactivity." Cellular Immunology 61, 2 (1981): 253-264. doi: 10.1016/0008-8749(81)90373-7.