IL-10 deficit correlates with chronic, hypersplenomegaly syndrome in male CBA/J mice infected with Schistosoma mansoni.
Twenty weeks after moderate level infections with Schistosoma mansoni, approximately 20% of male CBA/J mice develop hypersplenomegaly syndrome (HSS) while the rest present with moderate splenomegaly syndrome (MSS). HSS and MSS mice differ pathophysiologically (degree of splenomegaly, anaemia, ascites, periportal fibrosis, portal hypertension) and immunologically with regard to antibodies (idiotypic expression, isotype levels) to schistosome soluble egg antigens (SEA), and spleen cell phenotypic profiles. This study compared in vitro proliferative responses and IL-2, IFN gamma, IL-4, and IL-10 production by spleen cells from uninfected mice and mice with acute (8 wk), MSS or HSS schistosomiasis mansoni, upon exposure to anti-CD3 epsilon or SEA, Spleen cells from uninfected mice produce Il-2 to anti-CD3 epsilon but exposure of cells from all three groups of infected mice to anti-CD3 epsilon or SEA led to only very low levels of supernatant IL-2. Anti-CD3 epsilon- or SEA-stimulated production of IFN gamma or Il-4, and anti-CD3 epsilon-stimulated production of IL-10, displayed similar patterns: highest cytokine production by cells from mice with acute infections and lower levels of production that did not differ between the two chronic groups. In contrast, while SEA-stimulated IL-10 production was again highest with cells from mice with acute infections, spleen cells from mice with MSS produced significantly more IL-10 than did those from mice with HSS. This association of low levels of antigen-induced IL-10 with severe pathology is consistent with the theory that IL-10 plays a role in the immunoregulation that occurs in chronic schistosomiasis.
Bosshardt
S C
SC
Immunology Branch, Centers for Disease Control and Prevention, USA Public Health Service, Atlanta, GA 30341, USA.
Freeman
G L
GL
Secor
W E
WE
Colley
D G
DG
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology; D017252:CD3 Complex / Q000276:immunology; D002455:Cell Division; D002908:Chronic Disease; D007371:Interferon-gamma / Q000032:analysis / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D007376:Interleukin-2 / Q000032:analysis / Q000378:metabolism; D015847:Interleukin-4 / Q000032:analysis / Q000378:metabolism; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D012550:Schistosoma mansoni; D012555:Schistosomiasis mansoni / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000473:pathology; D013163:Splenomegaly / Q000209:etiology / Q000276:immunology*; D013577:Syndrome
D000947:Antigens, Helminth; D017252:CD3 Complex; D007376:Interleukin-2; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma