CD4+ T cells from collagen-induced arthritic mice are essential to transfer arthritis into severe combined immunodeficient mice

Abstract

The role of T lymphocytes in the adoptive transfer of collagen-induced arthritis (CIA) in DBA/1J mice to severe combined immunodeficient (SCID) mice was investigated. Spleen cells from non-immunized, type I collagen (CI) or type II collagen (CII)-immunized DBA/1J mice were injected into SCID mice which lack functional T and B cells. Specific antigenic stimulation of arthritogenic cells was required since only lymphocytes from arthritic CIA mice plus simultaneous administration of CII transferred arthritis to 11 of 12 SCID mice with a marked increase in CII antibody titre. However, CI-immunized or non-immunized DBA/1J mice cells did not induce arthritis in SCID mice. SCID recipients of pre-arthritic CIA lymphocytes presented increase in CII antibody, but showed no clinical signs of arthritis, suggesting that antibodies to CII alone can not induce CIA. Depletion of CD4+ T cells inhibited the transfer of arthritis to SCID mice, with a decrease in CII antibody titre in chimaeras. In contrast, depletion of CD8+ T cells enhanced the onset of arthritis in SCID mice. The results imply that CD4+ T cells are required for the induction of CIA. In addition, CD8+ T cells might have a suppressive role in the etiology of this disease. It is probable that memory CD4+ T cells stimulate production of antibodies to CII and subsequent arthritis. This study clarifies the role of T lymphocytes in the transfer of CIA to SCID mice.