The role of host (endogenous) T cells in chronic graft-versus-host autoimmune disease

Fangqi Chen, Michael A. Maldonado, Michael P. Madaio, Robert A. Eisenberg

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Chronic graft-vs-host (cGVH) disease induced by the transfer of Ia- incompatible spleen cells from one normal mouse strain (such as B6.C- H2(bm12)/KhEg (bm12)) to another (such as C57BL/6) causes an autoimmune syndrome resembling systemic lupus erythematosus (SLE). The role of host- derived T cells in this response is not obvious. Previous reports suggested that host T cells might serve to down-regulate the autoimmune syndrome. To address this issue more definitively, we used CD4 knockout (KO) or CD8KO C57BL/6 (B6) mice as recipients in the bm12→C57B6 cGVH model. CD4KO B6 mice injected with allogeneic bm12 spleen cells (bm12→CD4KO group) showed no evidence of cGVH disease. They made no detectable autoantibodies, including anti-chromatin, anti-dsDNA, anti-ssDNA, and rheumatoid factor. They survived at least 20 wks after induction of cGVH disease; and they did not develop nephritis, based on the absence of detectable levels of proteinuria and normal renal histology at the time of sacrifice. By contrast, CD8KO B6 mice (bm12→CD8KO group) and normal B6 mice (bm12→B6 group) injected with bm12 spleen cells generally showed similar levels of mortality, nephritis, and autoantibodies, although the autoantibody titers declined somewhat after week 8 in the bm12→CD8KO group. Control groups of recipients injected with B6 spleen cells showed no induction of autoantibodies. A surprising finding, however, was that the B6→CD8KO group developed severe histologic glomerulonephritis in the absence of autoantibodies and with decreased immune deposits. These results indicate that endogenous (host) CD4+ T cells play an essential role in the cGVH autoimmune syndrome.

Original languageEnglish (US)
Pages (from-to)5880-5885
Number of pages6
JournalJournal of Immunology
Volume161
Issue number11
StatePublished - Dec 1 1998
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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    Chen, F., Maldonado, M. A., Madaio, M. P., & Eisenberg, R. A. (1998). The role of host (endogenous) T cells in chronic graft-versus-host autoimmune disease. Journal of Immunology, 161(11), 5880-5885.