Production of alloreactive T-cell lymphomas

Abstract

Experiments predicting^1,2 or demonstrating lymphomagenesis in mice undergoing graft-versus-host (G-v-H) or chronic immunological reactions have been reported^3–5. In such cases, lymphomagenesis seemed to operate through the agency of activated murine leukaemia viruses (MuLV) and occurred only after very long latent periods, and most (but not all) lymphomas were of host origin⁴. No attempts were made in these studies to assess the relative role of T-cell subpopulations in lymphomagenesis. We have proposed elsewhere that certain MuLV-induced T lymphomas might be the progeny of that subset of normal thymocytes bearing antigen specific T-cell receptors for MuLV envelope antigens^6–10. Further, the MuLV binding to these cells provides both a portal of infection and a mitogenic signal^6,9,10. These cells and their thymic progeny would be subject to continuous restimulation by the endogenously produced MuLV envelope glycoproteins, and thus the apparent and “uncontrolled” proliferation of the cells would be due to their inability to resolve the viral infection and escape the resultant antigenic microenvironment. This receptor-mediated leukaemogenesis hypothesis predicts that any T-cell clone that cannot escape its stimulating antigens would appear to be lymphomagenic in that environment. Recent experiments in our laboratory have demonstrated that unique clones of strain A alloreactive T cells exist which can recognise hybrid mixed lymphocyte reaction (MLR)-stimulating determinants present on (C57B16 × A/J)F₁ (B6A) stimulator spleen cells^11–15. A variety of such clones have been isolated and characterised^13–15. We reasoned that, using these clones, it might be possible to generate alloreactive T-cell lymphomas by in vivo injection of these cells into hybrid B6A mice. We report our successful results here.