MHC-specific graft-protective and delayed-type hypersensitivity (DTH) suppressive activity of a CD4 + CD8 +, αβ T cell receptor (TCR) positive lymphoma isolated from a tolerant mouse

Abstract

Two lymphomas were found in, and isolated from A (H-2 a) mice in which permanent transplantation tolerance was induced to CBA (H-2 k) histocompatibility antigens by the neonatal injection of (CBAxA)F 1 spleen cells.They proved to be of recipient origin and were transferable to syngeneic A mice, growing as disseminated lymphomas (L33 and L46) and killing the recipients rapidly.Analysis of the cell surface antigens disclosed that both lymphomas had an immature T cell phenotype [Thy-1 +, CD5 +, CD3 low, TCRαβ low, CD4 low, CD8 high, heat-stable antigen (HSA) positive, and CD44 −, MHC class II −, CD45R −, sIg −, Gr-1 −, CD11b −]. Intraperitoneal (i.p.) injection of syngeneic A mice with viable L33 lymphoma cells resulted in a dose-dependent, significant prolongation of the mean survival times of «specific» CBA and MHC-identical B10.BR skin allografts as compared to the survival of appropriate grafts in non-lymphoma-bearing controls.The survival times of third party MHC-incompatible B10 (H-2 b) and B10.D2 (H-2 d) allografts were only slightly prolonged in A mice inoculated with L33 cells.The graft-protective effect was not abrogated if the proliferative capacity of the L33 cells was blocked by in vitro mitomycin C (MMC) pretreatment.Furthermore, the inoculation of L33 lymphoma into A mice significantly inhibited their DTH response to the sensitizing CBA histocompatibility antigens.In contrast, the L46 lymphoma had no effect on the survival of CBA allografts and the DTH reactivity.These data suggest that the CD4 +CD8 +TCRαβ + L33 T cell lymphoma originating from a neonatally tolerant mouse has a specific immunosuppressive effect on the in vivo reactivity of syngeneic mice to the tolerance-inducing (MHC class I) alloantigens.