Faculty Collaboration Database

Contribution of CD4+ and CD8+ T cells to graft-versus-host disease and graft-versus-leukemia reactivity after transplantation of MHC-compatible bone marrow. Bone Marrow Transplant 1991 Jul;8(1):51-8

Date

07/01/1991

Pubmed ID

1833016

Scopus ID

2-s2.0-0025784907 (requires institutional sign-in at Scopus site)   162 Citations

Abstract

A murine model of allogeneic bone marrow (BM) transplantation was used to determine the relative importance of CD4+ and CD8+ T cells in establishing donor T cell chimerism and in the development of graft-versus-host (GVH) and graft-versus-leukemia (GVL) reactivity. Mature donor T cells were essential for complete chimerism when host mice (AKR, H-2k) were conditioned with suboptimal irradiation (9 Gy = LD50). Transplantation of donor BM (B10.BR, H-2k) resulted in mixed chimerism, whereas mice given BM containing additional T cells developed into complete and stable chimeras. Depletion of T cell subsets was associated with an increase in the frequency of mixed chimerism. The incidence of lethal GVHD was dependent on the number of T cells added to the BM inoculum. Ex vivo depletion of CD4+ T cells eliminated GVH-associated mortality. Removal of CD8+ T cells had no effect on overall survival. In contrast to the GVH results, removal of either CD4+ or CD8+ T cells compromised GVL reactivity, indicating that an optimal GVL response required both CD4+ and CD8+ T cells. T cell-subset depletion did not interfere with the induction of donor-host tolerance in these chimeras and may have facilitated its development. The loss of GVH/GVL effector cells as a result of T cell depletion and the development of donor-host tolerance may act synergistically to prevent or suppress GVH and GVL reactivity.

Author List

Truitt RL, Atasoylu AA

Author

Robert L. Truitt PhD Emeritus Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Bone Marrow
Bone Marrow Transplantation
CD4 Antigens
CD8 Antigens
Chimera
Graft vs Host Disease
Histocompatibility
Leukemia, Experimental
Lymphocyte Depletion
Mice
T-Lymphocyte Subsets
T-Lymphocytes
T-Lymphocytes, Helper-Inducer
T-Lymphocytes, Regulatory