Immunopathogenesis and immunoregulation in schistosomiasis. Distinct chronic pathologic syndromes in CBA/J mice.
Inbred CBA/J mice with chronic (20-week) Schistosoma mansoni infections demonstrate two distinct syndromes. Hypersplenomegaly syndrome (HSS), characterized by a massive spleen, liver fibrosis, ascites, and anemia, resembles hepatosplenic human schistosomiasis, complete with portal hypertension and shunting. Moderate splenomegaly (MSS) syndrome, with less severe pathology, parallels most chronic human infections. Phenotypic analyses of spleen cells for CD44, CD62L, CD45RB, Ia, and CD25 indicate that HSS mice have more activated and memory CD4+ T cells than do MSS mice. HSS animals also have more B cells that highly express B7-2. Anti-CD3 stimulated spleen cells from 8-week or chronically infected mice produce IL-4 and IL-10 in a manner that appears not to involve the CD28/B7-2 costimulation pathway. By contrast IFN-gamma production is augmented in the presence of anti-CD28 and decreased in the presence of anti-B7-2. Infected mice make very little IL-2 to anti-CD3, even with added anti-CD28. As cytokines affect resultant B-cell responses and HSS and MSS mice display distinctive isotypes, differential regulatory or anergy hypotheses may best explain MSS/HSS differences.
Freeman
G L
GL
Division of Parasitic Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30341, USA.
Montesano
M A
MA
Secor
W E
WE
Colley
D G
DG
Howard
M J
MJ
Bosshardt
S C
SC
D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D006975:Hypertension, Portal / Q000209:etiology; D007136:Immunoglobulins / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D016131:Lymphocyte Subsets / Q000276:immunology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013163:Splenomegaly; D013601:T-Lymphocytes / Q000276:immunology
D000909:Antibodies, Helminth; D016207:Cytokines; D007136:Immunoglobulins; D007378:Interleukins; D007371:Interferon-gamma