INFECTION-ACTIVATED T-LYMPHOCYTES RESIST NITRIC OXIDE-MEDIATED IMMUNOSUPPRESSION IN THE COURSE OF FRANCISELLA-TULARENSIS 15L EXPERIMENTAL-INFECTION

Study of the inhibition of splenocyte proliferation stimulated by conc anavalin A (Con A), induced by Francisella tularensis 15L infection, s howed that immunosuppression is mediated by nitric oxide (NO), A certa in fraction of cells, however, resist the antiproliferative activities of NO and these were characterized as Thy-1.2 positive infection-acti vated T lymphocytes, The importance of this phenomenon for the develop ment of specific anti-infectious immunity was studied further in natur ally resistant and susceptible mouse strains. The naturally resistant mouse strain (C57BL/10) was characterized by early production of NO an d depressed splenocyte responsiveness to the mitogen. Early production of NO prevented activation of certain fractions of T lymphocytes, Hen ce the antibodies of these animals were only directed against three ma in F, tularensis antigens, Late or reduced release of NO from activate d macrophages of susceptible strains (C3H/He and BALB/c) on the other hand was accompanied by late or reduced immunosuppression, This result ed in polyclonal activation of the immune system because the antibodie s of these mice reacted with 6-12 compounds of the tularaemic antigen. The difference in heterogeneity of specific antibodies was not caused by a defect in the clonal network, as both the susceptible and resist ant strains responded similarly to inactivated F. tularensis antigen.