ROLES OF GAMMA-INTERFERON AND OTHER CYTOKINES IN SUPPRESSION OF THE SPLEEN-CELL PROLIFERATIVE RESPONSE TO CONCANAVALIN-A AND TOXOPLASMA ANTIGEN DURING ACUTE TOXOPLASMOSIS

Citation
E. Candolfi et al., ROLES OF GAMMA-INTERFERON AND OTHER CYTOKINES IN SUPPRESSION OF THE SPLEEN-CELL PROLIFERATIVE RESPONSE TO CONCANAVALIN-A AND TOXOPLASMA ANTIGEN DURING ACUTE TOXOPLASMOSIS, Infection and immunity, 63(3), 1995, pp. 751-756
Citations number
36
Categorie Soggetti
Immunology,"Infectious Diseases
Journal title
ISSN journal
00199567
Volume
63
Issue
3
Year of publication
1995
Pages
751 - 756
Database
ISI
SICI code
0019-9567(1995)63:3<751:ROGAOC>2.0.ZU;2-9
Abstract
Suppressed splenocyte proliferation in response to mitogen and toxopla sma lysate antigen (TLA) is observed in mice acutely infected with Tox oplasma gondii. Recently, we reported that N-G-monomethyl-L-arginine ( NMMA), an inhibitor of reactive nitrogen intermediate (RNI) production , partially restored proliferative responses of splenocytes from infec ted mice. In the present study we have examined the effect of NMMA on production of cytokines by splenocytes from mice acutely infected with T. gondii and assessed the role of gamma interferon (IFN-gamma) and i nterleukin-10 (IL-10) in the RNI-mediated suppression. Stimulation wit h concanavalin A (ConA) or TLA of splenocytes from CBA/Ca mice infecte d for 7 days resulted in increased production of IFN-gamma, IL-4 and I L-10 but reduced levels of IL-2 when compared with cultures of splenoc ytes from uninfected mice. Whereas addition of NMMA did not alter leve ls of cytokines produced by splenocytes from uninfected mice, splenocy tes from infected mice stimulated with ConA produced significantly hig her levels of IL-10 and reduced levels of IL-2 and IL-4. Addition of a nti-IFN-gamma monoclonal antibodies to cultures of spleen cells from m ice infected for 7 or 14 days remarkably decreased the levels of nitri te and resulted in a 47- and 4-fold increase in proliferation induced by stimulation with ConA or TLA, respectively. Anti-IL-10 did not redu ce levels of nitrite produced in culture but did result in a fourfold increase in the proliferative response of splenocytes from mice infect ed for 14 days. In vivo administration of anti-IFN-gamma or anti-IL-10 monoclonal antibodies to infected mice partially restored ex vivo spl een cell proliferative responses by approximately 40 and 15%, respecti vely. Our data indicate that IFN-gamma is important in inducing the RN I-mediated immunosuppression, which, in turn, affects production of cy tokines by splenocytes. Our data also demonstrate that IL-IO is involv ed in the suppression observed but that this activity is independent o f RNI.