Host NKT cells can prevent graft-versus-host disease and permit graft antitumor activity after bone marrow transplantation

Asha Pillai, Tracy I. George, Suparna Dutt, Pearline Teo, Samuel Strober

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

Allogeneic bone marrow transplantation is a curative treatment for leukemia and lymphoma, but graft-vs-host disease (GVHD) remains a major complication. Using a GVHD protective nonmyeloablative conditioning regimen of total lymphoid irradiation and antithymocyte serum (TLI/ATS) in mice that has been recently adapted to clinical studies, we show that regulatory host NKT cells prevent the expansion and tissue inflammation induced by donor T cells, but allow retention of the killing activity of donor T cells against the BCL1 B cell lymphoma. Whereas wild-type hosts given transplants from wild-type donors were protected against progressive tumor growth and lethal GVHD, NKT cell-deficient CD1d-/- and Jα-18-/- host mice given wild-type transplants cleared the tumor cells but died of GVHD. In contrast, wild-type hosts given transplants from CB8-/- or perforin-/- donors had progressive tumor growth without GVHD. Injection of host-type NKT cells into Jα-18-/- host mice conditioned with TLI/ATS markedly reduced the early expansion and colon injury induced by donor T cells. In conclusion, after TLI/ATS host conditioning and allogeneic bone marrow transplantation, host NKT cells can separate the proinflammatory and tumor cytolytic functions of donor T cells.

Original languageEnglish (US)
Pages (from-to)6242-6251
Number of pages10
JournalJournal of Immunology
Volume178
Issue number10
DOIs
StatePublished - May 15 2007
Externally publishedYes

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Natural Killer T-Cells
Graft vs Host Disease
Bone Marrow Transplantation
Lymphatic Irradiation
Transplants
T-Lymphocytes
Homologous Transplantation
Neoplasms
Serum
Tissue Expansion
Perforin
B-Cell Lymphoma
Growth
Lymphoma
Colon
Leukemia
Inflammation
Injections
Wounds and Injuries

ASJC Scopus subject areas

  • Immunology

Cite this

Host NKT cells can prevent graft-versus-host disease and permit graft antitumor activity after bone marrow transplantation. / Pillai, Asha; George, Tracy I.; Dutt, Suparna; Teo, Pearline; Strober, Samuel.

In: Journal of Immunology, Vol. 178, No. 10, 15.05.2007, p. 6242-6251.

Research output: Contribution to journalArticle

Pillai, Asha ; George, Tracy I. ; Dutt, Suparna ; Teo, Pearline ; Strober, Samuel. / Host NKT cells can prevent graft-versus-host disease and permit graft antitumor activity after bone marrow transplantation. In: Journal of Immunology. 2007 ; Vol. 178, No. 10. pp. 6242-6251.
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