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In vivo effects of deoxyspergualin (NKT-01) on lymphocyte activation in response to alloantigens
Y Yoshikawa1, H Uchida, H Kuroda
1Central Research Laboratories, Takara Shuzo Co., Ltd., Shiga, Japan.
We studied the effects of deoxyspergualin (NKT-01) on the events of lymphocyte activation in vivo by inoculating mice in the footpad with allogeneic spleen cells, and compared the effects with those of cyclosporin A (CyA). The administration of NKT-01 increased the numbers of cells recovered from the popliteal lymph node (PLN) 7 days after inoculation, but inhibited the proliferation of these cells in the presence of exogenous interleukin 2 (IL-2). NKT-01 enhanced IL-2 production, but suppressed the production of macrophage activating factor (MAF) in the mixed lymphocyte reaction between the PLN cells and allogeneic spleen cells treated with mitomycin C. CyA decreased the numbers of PLN cells little, and suppressed the response to exogenous IL-2 and the production of both IL-2 and MAF. Results with tumor cells used as allogeneic cells suggested that there was a close relationship between the suppression of MAF production by NKT-01 and its inhibition of allograft rejection. The findings showed that NKT-01 inhibited both the MAF production by and the response to IL-2 of PLN cells, and that these effects were involved in the suppression of allograft rejection by NKT-01.
We studied the effects of deoxyspergualin (NKT-01) on the events of lymphocyte activation in vivo by inoculating mice in the footpad with allogeneic spleen cells, and compared the effects with those of cyclosporin A (CyA). The administration of NKT-01 increased the numbers of cells recovered from the popliteal lymph node (PLN) 7 days after inoculation, but inhibited the proliferation of these cells in the presence of exogenous interleukin 2 (IL-2). NKT-01 enhanced IL-2 production, but suppressed the production of macrophage activating factor (MAF) in the mixed lymphocyte reaction between the PLN cells and allogeneic spleen cells treated with mitomycin C. CyA decreased the numbers of PLN cells little, and suppressed the response to exogenous IL-2 and the production of both IL-2 and MAF. Results with tumor cells used as allogeneic cells suggested that there was a close relationship between the suppression of MAF production by NKT-01 and its inhibition of allograft rejection. The findings showed that NKT-01 inhibited both the MAF production by and the response to IL-2 of PLN cells, and that these effects were involved in the suppression of allograft rejection by NKT-01.