The mouse immune response to human fibrinogen reveals an autoimmune component against mouse fibrinogen.
The present experiments were carried out to analyze whether immunization of mice with human fibrinogen would induce autoimmunity like other heterologous proteins such as collagen type II, thyroglobulin or myelin basic protein. Our results demonstrate that human fibrinogen induces very strong immune responses in all mouse strains analyzed. Autoimmune responses with short-term memory to mouse fibrinogen are induced in genetically susceptible mice. These autoimmune Th2-type responses induce splenomegaly, enhanced coagulation times, and production of rheumatoid factors. The short-lived autoimmune memory was not regulated by either suppressor T cells or exhaustion of immune cells; rather this potentially dangerous autoimmune response was regulated by unknown, antigen-specific feedback mechanisms (they do not influence immune responses to proteins like HSA and OA in the same mice). Such feedback mechanisms were not found in the immune responses to other heterologous proteins inducing significant cross-reactive autoimmunity such as collagen type II, thyroglobulin, or myelin basic protein.
Rubin
Bent
B
CNRS UMR 5165, CHU de Purpan, 31059 Toulouse Cedex 03, France. bent.rubin@istmt.cnrs.fr
Matron
Catherine
C
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000915:Antibody Affinity / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D001168:Arthritis / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D018920:Coculture Techniques; D003429:Cross Reactions / Q000276:immunology; D005260:Female; D005340:Fibrinogen / Q000276:immunology*; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007114:Immunization; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008136:Longevity / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D015375:Receptors, Interleukin-2 / Q000276:immunology; D012217:Rheumatoid Factor / Q000097:blood; D013163:Splenomegaly / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014914:Whole Blood Coagulation Time
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D015847:Interleukin-4; D005340:Fibrinogen; D012217:Rheumatoid Factor