More MS news articles for June 2002

Induction of Autoantibody Production Is Limited in Nonautoimmune Mice

J Immunol 2002 Jul 1;169(1):587-594
Singh RR, Ebling FM, Albuquerque DA, Saxena V, Kumar V, Giannini EH, Marion TN, Finkelman FD, Hahn BH.
Departments of. Internal Medicine and Pediatrics, University of Cincinnati College of Medicine and Veterans Affairs Medical Center, Cincinnati, OH 45220. Division of Rheumatology, University of California, Los Angeles, School of Medicine, Los Angeles, CA 90095. La Jolla Institute of Allergy and Immunology, San Diego, CA 92121. University of Tennessee, Memphis, TN 38163.

Many individuals develop a single or a few brief episodes of autoimmunity from which they recover.

Mechanisms that quell pathologic autoimmunity following such a breakdown of self-tolerance are not clearly understood.

In this study, we show that in nonautoimmune mice, dsDNA-specific autoreactive B cells exist but remain inactive.

This state of inactivation in dsDNA-specific B cells could be disrupted by autoreactive Th cells; in this case T cells that react with peptides from the V(H) region of anti-DNA Abs (hereafter called anti-V(H) T cells).

Immunization with anti-DNA mAb, its gamma-chain or peptides derived from its V(H) region induced anti-V(H) Th cells, IgG anti-dsDNA Ab, and proteinuria.

The breakdown of B cell tolerance in nonautoimmune mice, however, was short-lived: anti-DNA Ab and nephritis subsided despite subsequent immunizations.

The recovery from autoimmunity temporally correlated with the appearance of T cells that inhibited anti-DNA Ab production.

Such inhibitory T cells secreted TGFbeta; the inhibition of anti-DNA Ab production by these cells was partly abolished by anti-TGFbeta Ab.

Even without immunization, nonautoimmune mice possess T cells that can inhibit autoantibody production.

Thus, inhibitory T cells in nonautoimmune mice may normally inhibit T-dependent activation of autoreactive B cells and/or reverse such activation following stimulation by Th cells.

The induction of such inhibitory T cells may play a role in protecting nonautoimmune mice from developing chronic autoimmunity.