Cutting edge: Sustained expansion of CD8(+) T cells requires CD154 expression by Th cells in acute graft versus host disease

Brief treatment with alpha CD154 Ab has been shown to prevent acute graft v ersus host disease (aGvHD), me extend these data to show that in the absenc e of CD154 function, donor T cells are unable to expand or generate high le vel anti-host CTL activity, Using transgenic (Tg) alloreactive CD8(+) T cel ls adoptively transferred into allogeneic recipients, we show that short-te rm 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 alpha CD40. While CD40 agonism could enhance short-term expansion, sustained expa nsion of CD8(+) Tg T cells required bona fide CD154-expressing CD4(+) allor eactive Th cells. While CD154 was necessary for CD8(+) Tg T cell sustained expansion, IL-2 was also implicated as essential. These observations sugges t alpha CD154 therapy in GvHD is effective because the treatment causes an abortive CD8 alloresponse leading to the exhaustion or deletion of alloreac tive CD8(+) clones preventing the development of disease.