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 language | English (US) |
|---|---|
| Pages (from-to) | 6242-6251 |
| Number of pages | 10 |
| Journal | Journal of Immunology |
| Volume | 178 |
| Issue number | 10 |
| DOIs | |
| State | Published - May 15 2007 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Host NKT cells can prevent graft-versus-host disease and permit graft antitumor activity after bone marrow transplantation
AU - Pillai, Asha
AU - George, Tracy I.
AU - Dutt, Suparna
AU - Teo, Pearline
AU - Strober, Samuel
PY - 2007/5/15
Y1 - 2007/5/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=34248172955&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34248172955&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.178.10.6242
DO - 10.4049/jimmunol.178.10.6242
M3 - Article
C2 - 17475852
AN - SCOPUS:34248172955
VL - 178
SP - 6242
EP - 6251
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 10
ER -