Effect of allogeneic challenge dose and cyclophosphamide treatment on the development of delayed-type hypersensitivity and cell-mediated cytotoxicity.

Abstract

Mice were challenged with high (10(8)) or low (10(4)) numbers of allogenic tumor cells and assessed for cellular immunity. The responses obtained indicated that high dose challenge produced both delayed-type hypersensitivity (DTH) and cell-mediated cytotoxic reactivity (DCMC), while low dose challenge produced DTH, an apparent suppressive effect, and little or no DCMC. Pretreatment with 100 mg/kg of cyclophosphamide (CTX) 3 d before antigen failed to alter this pattern, but treatment 3 d after antigen administration abrogated both DTH and DCMC. Animals given a combined modulating protocol consisting of an initial low dose challenge followed on day 3 by CTX treatment and day 6 by a high dose challenge developed DCMC in the presence of a greatly reduced or absent DTH response. These results demonstrate the differential effects of allogeneic challenge dose on the development of cellular immunity; the differential effects of CTX treatment given prior to or following alloimmunization, and demonstrate how these effects can be combined to modulate the immune response by selectively activating subpopulations of T-lymphocytes.