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 bloo d 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 chi meras. 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% du ring 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 indi viduals with or without exogenous rIL-2 administration. Thus, human rI L-2 expanded autoreactive clones involved in the production of RF in t he SCID-RA chimeras. The present study provides a novel approach to es tablish an in vivo SCID-RA model to study the cellular and molecular m echanisms involved in the production of RF and development of a RA-lik e lesion. (C) 1995 Academic Press, Inc.