Inoculation of human interleukin-17 gene-transfected meth-A fibrosarcoma cells induces T cell-dependent tumor-specific immunity in mice

Objective: The biological activities of interleukin-17 (IL-17), a newly clo ned cytokine, have not been fully elucidated. The present study was designe d to assess the in vitro and in vivo effect of transfecting the IL-17 gene into tumor cells. Methods: A complementary DNA (cDNA) encoding human IL-17 (hIL-17) was obtained by polymerase chain reaction amplification from the h uman CD4+ T cell cDNA library and inserted into the plasmid pRc/cytomegalov irus to construct an expression vector for the hIL-17 gene. Murine Meth-A f ibrosarcoma cells were transfected with the hIL-17 gene using the lipofecti n method. The hIL-17 gene-expressing clone (Meth-A/IL-17) was selected and analyzed for cytokine expression by Northern blot. Results: There was no si gnificant difference in the in vitro proliferation rate among parent Meth-A , cells transfected with vector alone and Meth-A/IL-17 cells. When the tumo r cells were transplanted subcutaneously into BALB/c nude (nu+/nu+) mice, t here was no difference in in vivo growth rates among the three cell lines. Challenge with tumor cells in conventional BALB/c mice, however, resulted i n the rejection of Meth-A/IL-17 cells, but the other two lines did grow. Af ter immunization with Meth-A/IL-17 cells, the mice were rechallenged by par ent Meth-A or syngeneic MOPC-104E plasmacytoma cells; the immunized mice re jected the Meth-A cells, but not the MOPC-104E cells. Injecting the anti-th y 1,2 (CD90), anti-CD4 or anti-CD8 monoclonal antibody into conventional BA LB/c mice resulted in the resumption of in vivo growth of Meth-A/IL-17 cell s, but injecting the anti-asialo GM1 antibody did not. Furthermore, flow cy tometric analysis demonstrated a significant increase in the expression of major histocompatibility complex (MHC) class I and class II antigens and ly mphocyte function-associated antigen-1 on Meth-A/IL-17 cells. Conclusion: M eth-A cells transfected with the hIL-17 gene can induce tumor-specific anti tumor immunity by augmenting the expression of MHC class I and II antigens, and both CD4+ and CD8+ T cells may play important roles in inducing antitu mor immunity, suggesting the possibility of developing a tumor vaccine inco rporating IL-17-transfected tumor cells. Copyright (C) 2001 S. Karger AG, B asel.