Allosensitized helper and cytotoxic T-lymphocyte clones differentially modulate endotoxin-stimulated macrophage function.
Alterations in macrophage function may render the immunocompromised host more susceptible to infectious complications. Although allograft recipients are at increased risk of infection primarily because of pharmacologic immunosuppression, whether the process of allosensitization per se alters this risk is unknown. We therefore studied the effects of cloned allosensitized murine helper or cytotoxic T cells on both interleukin 1 (IL-1) and prostaglandin E2 (PGE2) production by syngeneic resident murine peritoneal macrophages. Endotoxin (lipopolysaccharide [LPS]) stimulated both IL-1 and PGE2 production in macrophages. Cloned T cells alone, with or without LPS pretreatment, produced neither IL-1 nor PGE2. After 48 hours of coculture with LPS-treated macrophages, cloned helper cells augmented IL-1 release by macrophages but inhibited PGE2 production. In contrast, cytotoxic T cells not only reduced IL-1 production by macrophages but also potentiated PGE2 release. These effects were not observed when macrophages were not first exposed to LPS. Thus, endotoxin renders macrophages more susceptible to allosensitized "help" (increases IL-1, decreases PGE2) or "suppression" (decreases IL-1, increases PGE2) by cytotoxic T cells. We hypothesize that, even in the absence of immunosuppression, the process of allosensitization itself may modulate the response to sepsis by altering host macrophage function.
D000818:Animals; D002999:Clone Cells; D015232:Dinoprostone; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D007108:Immune Tolerance; D007114:Immunization; D007375:Interleukin-1 / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D011458:Prostaglandins E / Q000096:biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D004731:Endotoxins; D007375:Interleukin-1; D011458:Prostaglandins E; D015232:Dinoprostone