Cytokine regulation of the immune response to retrovirally induced t-cell lymphomas of nih-swiss mice

The retrovirus SL3-3 MuLV, a murine leukemia virus, induces T-cell lymphoma in virtually 100% of infected animals with short latency. The ability of SL3-3 MuLV to induce T-cell lymphomas in immunocompetent animals suggests a profound failure or dysregulation of the immune response to the viral infection and subsequent malignancy. The role of cytokines in regulating the immune response to viral infection and malignancy is not well understood. We have undertaken an investigation of end stage SL3-3 MuLV-induced T-cell lymphomas from NIH-Swiss mice in order to dissect the mechanism of immune dysregulation. RNA extracted from T-cell tumors of the thymus or spleen of infected animals, or from uninfected controls, was used for RT-PCR reactions to evaluate the relative levels of cytokine mRNAs present in tumors. Preliminary results indicate that the expression of IL-10, TGF-beta and TNF-alpha is markedly elevated in tumors as compared to uninfected control tissues. IFN-gamma and IL-2 mRNA levels were low or absent, despite a heavy tumor burden. Taken together, these results indicate that cytokines known to exert a suppressive effect on the immune system, i.e., IL-10 and TGF-beta, are actively expressed in tumor cells. A consequence of this may be the suppression of IL-2 and IFN-gamma, cytokines associated with increased cell mediated immunity and Thl response.