Elimination of CD4+ T cells in mice bearing an advanced sarcoma augments the antitumor action of interleukin-2.
Experiments were undertaken to determine whether the depletion of CD4+ T cells from mice bearing an advanced immunogenic SA-1 sarcoma would result in an enhanced ability of interleukin-2 (IL-2) to cause tumor regression. The results show that whereas IL-2 therapy given as a 5-day course starting on day 10 of tumor growth caused complete regression of the tumor, it failed to cause regression if started on day 15 of tumor growth. However, in mice depleted of CD4+ T cells by treatment with anti-CD4 monoclonal antibody (mAb), IL-2 therapy started on day 15 resulted in appreciable tumor regression in most animals, and the therapeutic effect was greatly increased if two consecutive courses of anti-CD4 mAb and IL-2 therapy were given. On the other hand, treatment with anti-CD4 mAb alone had no effect on tumor growth. It was shown that the therapeutic action of combination therapy with anti-CD4 mAb and IL-2 was mediated by CD8+ T cells, because the therapeutic effect was completely ablated in mice depleted of CD8+ T cells with anti-CD8 mAb. Taken together these results suggest that, at a late stage of growth of an immunogenic tumor, depletion of CD4+ T cells can enhance the antitumor effect of IL-2 therapy by releasing CD(8+)-T-cell-mediated immunity from T-cell-mediated suppression.
Rakhmilevich
A L
AL
Trudeau Institute, Saranac Lake, NY 12983.
North
R J
RJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007376:Interleukin-2 / Q000008:administration & dosage*; D008212:Lymphocyte Depletion; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D012513:Sarcoma, Experimental / Q000276:immunology*; D016019:Survival Analysis
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D007376:Interleukin-2