In vitro and in vivo recovery of IFN-gamma, but not IL-2, production by IL-12 in mice with plasma cell tumors.
We have previously found that T cells from mice bearing plasma cell tumors (PCT mice) demonstrate decreased proliferation as well as decreased production of the Th 1-associated cytokines IL-2 and IFN-gamma in response to polyclonal stimulation. In the present study, we have examined soluble factors as possible elements required to rescue this decreased proliferation and cytokine production by splenocytes from PCT mice. We find that the addition of supernatants from stimulated normal splenocytes has no effect on proliferation of IL-2 production by splenocytes from PCT mice. In contrast, these supernatants completely restore IFN-gamma production by splenocytes from PCT mice. We have found that IL-12 is responsible for the observed increase in IFN-gamma production because: (i) addition of anti-IL-12 antibody blocks this recovery of IFN-gamma production by these supernatants, (ii) the addition of recombinant IL-12 to cultures of splenocytes from PCT mice results in increased IFN-gamma production and (iii) in vivo treatment of PCT mice in IL-12 also results in increased IFN-gamma production by the subsequently activated splenocytes, but has little effect on proliferation or IL-2 production. These results demonstrate that both in vitro and in vivo, IL-12 selectively restores the decreased production of IFN-gamma by splenocytes from PCT mice.
Ruzek
M C
MC
Department of Microbiology, University of Minnesota, Minneapolis 55455, USA.
Mathur
A
A
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division; D002478:Cells, Cultured / Q000276:immunology; D017077:Culture Media, Conditioned; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010954:Plasmacytoma / Q000276:immunology*; D011994:Recombinant Proteins; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D017077:Culture Media, Conditioned; D007376:Interleukin-2; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma