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 concanavalin A (Con A), induced by Francisella tularensis 15L infection, showed that immunosuppression is mediated by nitric oxide (NO). A certain fraction of cells, however, resist the antiproliferative activities of NO and these were characterized as Thy-1.2 positive infection-activated T lymphocytes. The importance of this phenomenon for the development of specific anti-infectious immunity was studied further in naturally resistant and susceptible mouse strains. The naturally resistant mouse strain (C57BL/10) was characterized by early production of NO and depressed splenocyte responsiveness to the mitogen. Early production of NO prevented activation of certain fractions of T lymphocytes. Hence the antibodies of these animals were only directed against three main F. tularensis antigens. Late or reduced release of NO from activated macrophages of susceptible strains (C3H/He and BALB/c) on the other hand was accompanied by late or reduced immunosuppression. This resulted in polyclonal activation of the immune system because the antibodies 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 resistant strains responded similarly to inactivated F. tularensis antigen.
Hajdúch
M
M
Department of Paediatrics, Faculty of Medicine, Palacký University, and Faculty Hospital in Olomouc, Czech Republic. marian@risc.upol.cz
Nemcek
R
R
Vítek
P
P
Macela
A
A
Kovárová
H
H
D000818:Animals; D003114:Colony-Forming Units Assay; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006968:Hypersensitivity, Delayed; D007108:Immune Tolerance; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis / Q000276:immunology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D013045:Species Specificity; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D014406:Tularemia / Q000276:immunology* / Q000378:metabolism; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase