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Divisions of
*
Rheumatology and
Renal-Electrolyte and Hypertension, Department of Medicine, University of Pennsylvania Medical Center, Philadelphia, PA 19104
Chronic graft-vs-host (cGVH) disease induced by the transfer of
Ia-incompatible spleen cells from one normal mouse strain (such as
B6.C-H2bm12/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 (bm12CD4KO 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
(bm12CD8KO group) and normal B6 mice (bm12B6 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 bm12CD8KO group. Control
groups of recipients injected with B6 spleen cells showed no induction
of autoantibodies. A surprising finding, however, was that the
B6CD8KO 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.
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