Naslov
Factors governing the activation of adoptively transferred donor T cells infused after allogeneic bone marrow transplantation in the mouse

Autori
Duraković, Nadira ; Radojčić, Vedran ; Škarica, Mario ; Bezak, Karl B. ; Powell, J.D. ; Fuchs, E.J. ; Luznik, Leo

Izvornik
Blood (0006-4971) 109 (2007), 10; 4564-4574

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
allogeneic bone marrow transplant; donor T cells; GVL

Sažetak
Murine models of bone marrow transplantation were used to study the mechanisms governing the activation of donor lymphocyte infusions (DLIs) manifesting as lymphohematopoietic graft-versus-host (LH-GVH) and graft-versus-leukemia (GVL) reactivities. We demonstrate here that established mixed chimerism influences the potency of DLI-mediated alloreactivity only in the MHC-mismatched but not MHC-matched setting. In the MHC-matched setting, high levels (>or= 40%) of residual host chimerism correlated negatively with DLI-mediated alloreactivity irrespective of the timing of their administration, the donor's previous sensitization to host antigens, or the level of residual host APCs. In vivo administration of Toll-like receptor (TLR) ligands was required to maximize DLI-mediated LH-GVH and GVL reactivities in chimeras with low levels (<or= 15%) of residual host chimerism. In contrast, coadministration of DLI with antigen-presenting cell (APC) activators was insufficient to augment their LH-GVH response in the presence of high levels of host chimerism unless the host's T cells were transiently depleted. Together, these results show the cardinal influence of donor-host incompatibility on DLI-mediated GVH responses and suggest that in MHC-matched chimeras, the induction of optimal alloreactivity requires not only donor T cells and host APCs but also TLR ligands and in the presence of high levels of host chimerism depletion of host T cells.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA