B cells require "nurturing" by CD4 T cells during development in order to respond in chronic graft-versus-host model of systemic lupus erythematosus.
The murine chronic GVH (cGVH) model of SLE is induced by allo-recognition of foreign major histocompatibility complex (MHC) class II determinants. Previous studies have shown that syngeneic CD4(+) T cells are needed during B cell development in order to induce cGVH response in CD4KO mice. Our present studies show that B cells require "nurturing" by CD4 T cells through much of their ontogeny in order to respond to allo-signaling and become autoreactive. The nurturing process does not require antigen-specific cognate interactions between CD4 T cells and B cells. It is mediated by IL-4, but not IL-10, IL-6 and IFN-gamma. The CD4 T cell nurturing may be supplanted by large doses of IL-4 and/or by agonistic anti-CD40 mAb. Understanding the mechanism of this "nurturing" process may yield clues to the role of CD4 T cells in lupus and in host defense in general.
Choudhury
Arpita
A
Division of Rheumatology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cohen
Philip L
PL
Eisenberg
Robert A
RA
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001323:Autoantibodies / Q000097:blood; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D015704:CD4 Antigens / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D019013:CD40 Antigens / Q000819:agonists / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology / Q000652:urine; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology / Q000652:urine; D008213:Lymphocyte Activation / Q000276:immunology; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D011507:Proteinuria / Q000175:diagnosis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D012867:Skin / Q000473:pathology
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D015704:CD4 Antigens; D019013:CD40 Antigens; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D018398:Homeodomain Proteins; D011948:Receptors, Antigen, T-Cell; C064658:RAG-1 protein; D015847:Interleukin-4
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