Successful Transfer of Localized Autoimmunity with Positively Selected CD4⁺ Cells to scid Mice Lacking Functional B Cells

Abstract

T-cell function of athymic BALB/c-nu/nu (nude) mice can be corrected by implantation of a embryonic rat thymus graft (TG) under the renal capsule (TG nude mice). However, multiple organ-localized autoimmune diseases, such as oophoritis, Sjögren's syndrome like disease and gastritis, develop spontaneously in TG nude mice. Transfer of spleen cells from TG nude mice with such diseases leads to multiple localized autoimmune lesions with appearance of the corresponding autoantibodies in the recipient C.B-17-scid(SCID) mice. In the present study, removal of CD90⁺ or CD4⁺, but not CD8⁴ cells eliminated the transfer activity. Positively selected CD4⁺ cells proved capable of inducing lesions without the appearance of organ- specific autoantibodies, although the grade of lesions was lower than that in recipient mice that received untreated or CD8-depleted spleen cells. Target organs demonstrating CD4⁺ cell infiltration, generally expressed major histocompatibility complex (MHC) class II antigen (Ia) on their parenchymal cells. Injection of sera from TG nude mice with autoantibodies to SCID mice did not induce any pathogenic features in the autoantibody- target organs, although deposition of immunoglobulins in the corresponding target organs was observed. In such cases, no la antigens were expressed on the parenchymal cells. The data thus indicate that effector CD4⁺ cells can induce autoimmunity without B-cell help but that cooperation with functional B cells induces more severe tissue damage.

Key Words:

• Major histocompatibility complex class II antigens
• Autoimmunity
• scid mice
• CD4⁺ cells
• Thymus grafts