Mechanism by which Regulatory Rheumatoid Factor Prevents Experimental Autoimmune Encephalomyelitis

One mechanism that underlies protection from autoimmunity and avoidance of uncontrolled inflammation is the controlled contraction of lymphocyte expansion during the immune response. We identified regulatory rheumatoid factor (regRF), the production of which is associated with resistance to and remission of experimental autoimmune diseases. RegRF is anti-idiotypic antibodies to lymphocyte receptors against autoimmune disease-inducing antigens; at the same time, it is specific to epitopes in the hinge Fc fragments of IgG.

The aim of this study is to test the hypothesis that regRF prevents autoimmunity by limiting the expansion of lymphocytes.

To test this hypothesis, we used a model of experimental autoimmune encephalitis.

We found that in the lymph nodes that drain the injection site in rats producing regRF in response to immunization with myelin basic protein (MBP) the proportion of CD4+lymphocytes was lower than in rats in which MBP-immunization did not induce higher regRF levels. RegRF-containing plasma obtained from MBP-immunized rats induces complement-dependent killing of MBP-activated lymphocytes. Activated MBP-specific lymphocytes are not sensitive to the regRF-containing plasma of intact rats.

The regRF produced during the immune response is a specific control factor for the expansion of antigen-activated CD4+lymphocytes.