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*
Department of Microbiology, Dartmouth Medical School, Lebanon, NH 03756;
Department of Pediatrics, Division of Bone Marrow Transplantation, University of Minnesota, Minneapolis, MN 55455;
Diabetes Division, University of Massachusetts Medical School, Worcester, MA 01605; and
§
Department of Immunobiology, Yale University, New Haven, CT 06520
Brief treatment with 
CD154 Ab has been shown to prevent acute
graft versus host disease (aGvHD). We extend these data to show that in
the absence of CD154 function, donor T cells are unable to expand or
generate high level anti-host CTL activity. Using transgenic (Tg)
alloreactive CD8+ T cells adoptively transferred into
allogeneic recipients, we show that short-term expansion of the
CD8+ Tg T cells occurred in the absence of Th cells, and
this short-term expansion could be facilitated with an agonistic
CD40. While CD40 agonism could enhance short-term expansion,
sustained expansion of CD8+ Tg T cells required bona fide
CD154-expressing CD4+ alloreactive Th cells. While CD154
was necessary for CD8+ Tg T cell sustained expansion, IL-2
was also implicated as essential. These observations suggest CD154
therapy in GvHD is effective because the treatment causes an abortive
CD8 alloresponse leading to the exhaustion or deletion of alloreactive
CD8+ clones preventing the development of
disease.
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