Involvement of donor T-cell cytotoxic effector mechanisms in preventing allogeneic marrow graft rejection

Paul J. Martin, Yoshiki Akatsuka, Michael Hahne, George Sale

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Donor CD8 cells play a pivotal role in preventing allogeneic marrow graft rejection, possibly by generating cytotoxic effectors needed to eliminate recipient T cells remaining after the pretransplant conditioning regimen or by producing cytokines needed to support the growth and differentiation of hematopoietic stem cells. In the present study, we assessed the role of donor T-cell cytotoxic effector function as a mechanism for eliminating recipient CD8 cells that cause marrow graft rejection in mice. The ability to prevent rejection was minimally affected by the presence of a defect in Fas ligand binding or by the absence of granzyme B but was severely affected by the absence of perforin. Doubly mutant perforin- deficient, Fas ligand-defective CD8 cells were completely unable to prevent rejection. Our results indicate first that recipient CD8 effectors responsible for causing marrow graft rejection are sensitive to cytotoxicity mediated by both perforin- and Fas-ligand-dependent mechanisms, and second that donor T cells must have at least one functional cytotoxic mechanism to prevent allogeneic marrow graft rejection.

Original languageEnglish
Pages (from-to)2177-2181
Number of pages5
JournalBlood
Volume92
Issue number6
Publication statusPublished - 15-09-1998
Externally publishedYes

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T-cells
Graft Rejection
Grafts
Perforin
Fas Ligand Protein
Bone Marrow
T-Lymphocytes
Granzymes
Cytotoxicity
Hematopoietic Stem Cells
Stem cells
Cytokines
Defects
Growth

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Martin, P. J., Akatsuka, Y., Hahne, M., & Sale, G. (1998). Involvement of donor T-cell cytotoxic effector mechanisms in preventing allogeneic marrow graft rejection. Blood, 92(6), 2177-2181.
Martin, Paul J. ; Akatsuka, Yoshiki ; Hahne, Michael ; Sale, George. / Involvement of donor T-cell cytotoxic effector mechanisms in preventing allogeneic marrow graft rejection. In: Blood. 1998 ; Vol. 92, No. 6. pp. 2177-2181.
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Martin, PJ, Akatsuka, Y, Hahne, M & Sale, G 1998, 'Involvement of donor T-cell cytotoxic effector mechanisms in preventing allogeneic marrow graft rejection', Blood, vol. 92, no. 6, pp. 2177-2181.

Involvement of donor T-cell cytotoxic effector mechanisms in preventing allogeneic marrow graft rejection. / Martin, Paul J.; Akatsuka, Yoshiki; Hahne, Michael; Sale, George.

In: Blood, Vol. 92, No. 6, 15.09.1998, p. 2177-2181.

Research output: Contribution to journalArticle

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