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