REOVIRUS INFECTION IN CHICKENS PRIMES SPLENIC ADHERENT MACROPHAGES TOPRODUCE NITRIC-OXIDE IN RESPONSE TO T-CELL-PRODUCED FACTORS

In this study, we examined the mechanisms by which avian reovirus infe ction of chickens depresses in vitro proliferative responses of spleen cells to T cell mitogens. We showed an enhanced production of nitric oxide (NO) by phytohemagglutinin (PHA)-stimulated spleen cells from re ovirus-infected birds but not from virus-free birds. Since macrophages are a primary source of NO, we compared splenic adherent macrophages from virus-free and virus-exposed chickens. There was a fourfold incre ase in the number of adherent macrophages from the spleens of virus-ex posed chickens. Production of NO by macrophages from virus-exposed chi ckens required T-cell-produced factors and was not due to direct stimu lation of macrophages by PHA. Although T cell products were needed for NO production by macrophages, in an apparent paradox, we found signif icantly reduced levels of NO-inducing activity in the supernatants of PHA-stimulated spleen cells from virus-exposed chickens than in supern atants from PHA-stimulated normal spleen cells. Cocultures of adherent cells from infected chickens with normal spleen cells indicated that although macrophages secreted NO following PHA stimulation, macrophage s ultimately suppressed the continued production of NO-inducing factor s by normal spleen cells. We further showed in experiments utilizing N -G-monomethyl-L-arginine, an NO synthesis inhibitor, that NO was not r esponsible for the mitogenic inhibition of spleen cells from virus-exp osed chickens. In summary, our results indicated that following reovir us infection, macrophages are primed in vivo and activated in vitro by T-cell-produced factors. Despite the requirement of T cell cytokines for NO production, T cells did not proliferate to mitogenic stimuli, w hich indicated that the early events (i.e., cytokine secretion) but no t the late events (i.e., proliferation) of the T cell activation casca de were functional. Macrophage priming following reovirus infection ma y have important implications for impaired T cell responsiveness. (C) 1995 Academic Press, Inc.