Human recombinant IL-2 augments immunoglobulin and induces rheumatoid factor production by rheumatoid arthritis lymphocytes engrafted into severe combined immunodeficient mice.
Recombinant (r) human IL-2 was administered in vivo to improve homing and engraftment of rheumatoid arthritis (RA) patients' peripheral blood mononuclear cells (PBMC) into severe combined immunodeficient (SCID) mice. Human rIL-2 treatment resulted in augmented human Ig production and induced IgM rheumatoid factor (RF) of human origin in SCID-RA chimeras. The increment of human serum IgG in SCID-RA chimeras after IL-2 treatment ranged between 15 and 43% and for IgM between 50 and 98% during 2-8 weeks postengraftment. Human IgM-RF was detectable after 1 to 2 weeks after engraftment and persisted over a period of 10-13 weeks. No RF was produced in SCID mice engrafted with PBMC from healthy individuals with or without exogenous rIL-2 administration. Thus, human rIL-2 expanded autoreactive clones involved in the production of RF in the SCID-RA chimeras. The present study provides a novel approach to establish an in vivo SCID-RA model to study the cellular and molecular mechanisms involved in the production of RF and development of a RA-like lesion.
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston 77555.
R
R
Kaul
A
A
Sharma
J R
JR
Lisse
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P
Christadoss
D000328:Adult; D000368:Aged; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002678:Chimera; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D017710:Lymphocyte Transfusion; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012217:Rheumatoid Factor / Q000096:biosynthesis*; D013154:Spleen / Q000166:cytology / Q000276:immunology
D007136:Immunoglobulins; D007376:Interleukin-2; D011994:Recombinant Proteins; D012217:Rheumatoid Factor