No abstract

New World primates develop T-cell lymphomas on infection with Herpesvirus saimiri. To investigate the oncogenic potential of the Tip gene of Herpesvirus saimiri strain C488, we tried to establish transgenic mice that should express Tip under control of a constitutive promoter. Although transgene-positive embryos were found, lines could not be established. However, using a system in which the transgene has to be activated by a Cre recombinase-mediated deletion, we were able to obtain several Tip transgenic lines. At high expression levels, the mice developed T-cell lymphomas. Thus, Tip can induce lymphomas and is therefore very likely responsible for the oncogenicity of Herpesvirus saimiri.

Transgenic expression of apoptosis‐inducing molecules could be a strategy to protect cells and tissues from destruction by apoptosis‐susceptible effector T cells. Some evidence for the potencyof this approach has been obtained in mouse and rat transplantation models. However, limited data are available on the capacity of apoptosis‐inducing molecules to modulate human alloimmune responses. In this study we analyzed the in vitro consequences of an interaction of human T cells with allogeneic 293 cells and 293 transfectants stably expressing high levels of the apoptosis‐inducing CD95 ligand (CD95L). Both, CD95L– and CD95L+ 293 cells were able to activate allogeneic T cells as demonstrated by comparable CD25 expression at day 2 of culture. The analysisof viable T cells at day 7, however, revealed anti‐293 cytotoxic activity only in cultures that had been stimulated with CD95L– 293 cells. Alloactivated effector T cells lysed CD95L– and CD95L+ 293 targets with similar efficiency when tested in a 4‐h 51Cr‐release assay. Prolongation of the effector phase to 20 h resulted in a further increase in the destruction of CD95L– target cells, whereas lysis of CD95L+ targets remained low. These data suggest that genetically engineered expression of CD95L on cells or tissues could be an approach to control human T cell reactivity towards allografts. During the induction of an alloimmune response depletion of cytotoxic precursor cells may be obtained by overexpressing CD95L on stimulatory cells; CD95L expression on graft tissue might limit T cell‐mediated destruction of the transplant during the effector phase of the response.