HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kretz-Rommel, A. Articles by Rubin, R. L. Search for Related Content PubMed PubMed Citation Articles by Kretz-Rommel, A. Articles by Rubin, R. L.

Persistence of Autoreactive T Cell Drive Is Required to Elicit Anti-Chromatin Antibodies in a Murine Model of Drug-Induced Lupus¹

W. M. Keck Autoimmune Disease Center, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037

Long-term treatment with procainamide and numerous other medications is occasionally associated with the development of drug-induced lupus. We recently established a murine model for this syndrome by disrupting central T cell tolerance. Two intrathymic injections of procainamide-hydroxylamine (PAHA), a reactive metabolite of procainamide, into (C57BL/6 x DBA/2)F₁ mice resulted in the appearance of chromatin-reactive T cells and anti-chromatin autoantibodies. The current study explores in this model the role of autoreactive T cells in autoantibody production and examines why autoantibodies after a single intrathymic drug injection were much more limited in isotype and specificity. Injection of as few as 5000 chromatin-reactive T cells into naive, syngeneic mice induced a rapid IgM anti-denatured DNA response, while injection of at least 100-fold greater number of activated T cells was required for induction of IgG anti-chromatin Abs, suggesting that small numbers of autoreactive T cells can be homeostatically controlled. Mice subjected to a single intrathymic PAHA injection after receiving splenic B cells from an intrathymic PAHA-injected syngeneic donor also developed anti-chromatin Abs, but adoptive transfer of similarly primed T cells or of B cells without intrathymic PAHA injection of the recipient failed to produce an anti-chromatin response. However, anti-chromatin Abs developed after a single intrathymic PAHA injection in Fas-deficient C57BL/6-lpr/lpr mice, suggesting that activation-induced cell death limited autoimmunity in normal mice. Taken together, these results imply that chromatin-reactive T cells produced by intrathymic PAHA created a B cell population primed to somatically mutate and Ig class switch when subjected to a heavy load or second wave of autoreactive T cells.

This article has been cited by other articles:

				R L Rubin, D R Salomon, and R S Guerrero Thymus Function in Drug-Induced Lupus Lupus, November 1, 2001; 10(11): 795 - 801. [Abstract] [PDF]

				V. M. Lentz and T. Manser Self-limiting systemic autoimmune disease during reconstitution of T cell-deficient mice with syngeneic T cells: support for a multifaceted role of T cells in the maintenance of peripheral B cell tolerance Int. Immunol., November 1, 2000; 12(11): 1483 - 1497. [Abstract] [Full Text] [PDF]

				S A Huber, J Kupperman, and M K Newell Estradiol prevents and testosterone promotes Fas-dependent apoptosis in CD4+ Th2 cells by altering Bcl 2 expression Lupus, June 1, 1999; 8(5): 384 - 387. [Abstract] [PDF]