Central role for interleukin-4 in regulating nitric oxide-mediated inhibition of T-cell proliferation and gamma interferon production in schistosomiasis.
Schistosoma mansoni-infected wild-type (WT) mice develop a Th2 response and chronic disease. In contrast, infected interleukin-4 double-deficient (IL-4(-/-)) mice develop a Th1-like response and an acute, lethal syndrome. Disease severity in these animals correlates with excessive and prolonged production of nitric oxide (NO) associated with enhanced antigen-driven gamma interferon (IFN-gamma) production in the absence of IL-4. Strikingly, splenic lymphocytes from infected IL-4(-/-) mice failed to proliferate as well as those from infected WT mice following stimulation in vitro with antigen or anti-CD3 antibody. Contrary to antigen-driven IFN-gamma responses, anti-CD3 antibody stimulation of splenocytes resulted in significantly less IFN-gamma being produced by CD8 cells from infected IL-4(-/-) mice than by those from infected WT mice or normal mice. NO is largely responsible for the impaired T-cell functions in infected IL-4(-/-) mice, as inhibition of iNOS significantly enhanced proliferation and IFN-gamma production.
Patton
Elisabeth A
EA
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
La Flamme
Anne C
AC
Pedras-Vasoncelos
Joao A
JA
Pearce
Edward J
EJ
D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D007371:Interferon-gamma / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000276:immunology*; D012550:Schistosoma mansoni / Q000276:immunology; D012555:Schistosomiasis mansoni / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
D015847:Interleukin-4; D009569:Nitric Oxide; D007371:Interferon-gamma