Induction of granulomatous experimental autoimmune thyroiditis in IL-4 gene-disrupted mice.
To study the role of IL-4 in development of granulomatous experimental autoimmune thyroiditis (EAT), IL-4 gene-disrupted mice expressing the EAT-susceptible H-2k haplotype were generated and used for EAT induction. Spleen cells from mouse thyroglobulin (MTg) and LPS-primed IL-4(+/+) and IL-4(-/-) donors could induce severe granulomatous EAT when spleen cells were activated with MTg and anti-IL-2R mAb in the presence of IL-12. Thyroid lesions had extensive follicular cell proliferation, large numbers of histiocytes, polymorphonuclear leukocytes, and multinucleated giant cells, in addition to lymphocytes and other mononuclear cells. Expression of IFN-gamma gene mRNA and production of IFN-gamma by effector spleen cells stimulated with MTg and IL-12 were similar for both IL-4(+/+) and IL-4(-/-) mice. Although IL-4 was undetectable in IL-4(-/-) mice, expression of mRNA for IL-5, IL-10, and IL-13 and production of IL-5 by both MTg-activated spleen cells and anti-CD3-activated CD4+ T cells were comparable for cells from IL-4(+/+) and IL-4(-/-) mice, indicating that the absence of IL-4 did not prevent production of other Th2 cytokines. Production of MTg-specific IgG1 was very low or undetectable in IL-4(-/-) mice. IL-4 gene mRNA and MTg-specific IgG1 could be detected in IL-4(+/+) or IL-4(-/-) recipients only when they received effector cells from IL-4(+/+) donor mice, indicating that IL-4- and IgG1-secreting cells are of donor origin. These results demonstrate that IL-4 is not essential for development of granulomatous EAT.
Tang
H
H
Department of Internal Medicine, University of Missouri-Columbia School of Medicine, 65212, USA.
Sharp
G C
GC
Peterson
K E
KE
Braley-Mullen
H
H
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D006099:Granuloma / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000276:immunology; D018664:Interleukin-12 / Q000502:physiology; D015847:Interleukin-4 / Q000172:deficiency* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D018418:Th2 Cells / Q000276:immunology; D013954:Thyroglobulin / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000276:immunology*
D001323:Autoantibodies; D016207:Cytokines; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D012333:RNA, Messenger; D018664:Interleukin-12; D015847:Interleukin-4; D013954:Thyroglobulin