Abstract
Objective: T cells that undergo lymphopenia-induced proliferation (LIP) are characterized by greater effector and anti-tumor function than naïve T cells. But the ability of these T cells in causing graft-versus-host disease (GVHD) is not known. Methods: We tested the hypothesis that donor T cells that had undergone LIP would cause more severe GVHD than naïve T cells by utilizing well-characterized murine experimental models of allogeneic bone marrow transplantation (BMT). Results: Contrary to our hypothesis, LIP of donor T cells under either noninflammatory or irradiated conditions caused significantly reduced GVHD as determined by survival, clinical, pathologic, and biochemical parameters than naïve T cells. Compared to naïve donor T cells, LIP T cells demonstrated reduced expansion in vivo and in vitro after allogeneic BMT. The reduction in GVHD mortality and severity was observed across multiple strains after allogeneic BMT. In vivo mechanistic studies by cell depletion demonstrated an increase in the CD44hi "memory" phenotype T cells and not the CD4+CD25+ T cell subset to be critical for the reduction in GVHD. Conclusions: These data demonstrate that LIP of T cells regulates acute GVHD severity in contrast to their ability to cause increased allograft rejection, autoimmunity, or anti-tumor immunity.
| Original language | English |
|---|---|
| Pages (from-to) | 274-286 |
| Number of pages | 13 |
| Journal | Experimental Hematology |
| Volume | 35 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 2007 |
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ASJC Scopus subject areas
- Cancer Research
- Cell Biology
- Genetics
- Hematology
- Oncology
- Transplantation
Cite this
Lymphopenia-induced proliferation of donor T cells reduces their capacity for causing acute graft-versus-host disease. / Maeda, Yoshinobu; Tawara, Isao; Teshima, Takanori; Liu, Chen; Hashimoto, Daigo; Matsuoka, Ken-ichi; Tanimoto, Mitsune; Reddy, Pavan.
In: Experimental Hematology, Vol. 35, No. 2, 02.2007, p. 274-286.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Lymphopenia-induced proliferation of donor T cells reduces their capacity for causing acute graft-versus-host disease
AU - Maeda, Yoshinobu
AU - Tawara, Isao
AU - Teshima, Takanori
AU - Liu, Chen
AU - Hashimoto, Daigo
AU - Matsuoka, Ken-ichi
AU - Tanimoto, Mitsune
AU - Reddy, Pavan
PY - 2007/2
Y1 - 2007/2
N2 - Objective: T cells that undergo lymphopenia-induced proliferation (LIP) are characterized by greater effector and anti-tumor function than naïve T cells. But the ability of these T cells in causing graft-versus-host disease (GVHD) is not known. Methods: We tested the hypothesis that donor T cells that had undergone LIP would cause more severe GVHD than naïve T cells by utilizing well-characterized murine experimental models of allogeneic bone marrow transplantation (BMT). Results: Contrary to our hypothesis, LIP of donor T cells under either noninflammatory or irradiated conditions caused significantly reduced GVHD as determined by survival, clinical, pathologic, and biochemical parameters than naïve T cells. Compared to naïve donor T cells, LIP T cells demonstrated reduced expansion in vivo and in vitro after allogeneic BMT. The reduction in GVHD mortality and severity was observed across multiple strains after allogeneic BMT. In vivo mechanistic studies by cell depletion demonstrated an increase in the CD44hi "memory" phenotype T cells and not the CD4+CD25+ T cell subset to be critical for the reduction in GVHD. Conclusions: These data demonstrate that LIP of T cells regulates acute GVHD severity in contrast to their ability to cause increased allograft rejection, autoimmunity, or anti-tumor immunity.
AB - Objective: T cells that undergo lymphopenia-induced proliferation (LIP) are characterized by greater effector and anti-tumor function than naïve T cells. But the ability of these T cells in causing graft-versus-host disease (GVHD) is not known. Methods: We tested the hypothesis that donor T cells that had undergone LIP would cause more severe GVHD than naïve T cells by utilizing well-characterized murine experimental models of allogeneic bone marrow transplantation (BMT). Results: Contrary to our hypothesis, LIP of donor T cells under either noninflammatory or irradiated conditions caused significantly reduced GVHD as determined by survival, clinical, pathologic, and biochemical parameters than naïve T cells. Compared to naïve donor T cells, LIP T cells demonstrated reduced expansion in vivo and in vitro after allogeneic BMT. The reduction in GVHD mortality and severity was observed across multiple strains after allogeneic BMT. In vivo mechanistic studies by cell depletion demonstrated an increase in the CD44hi "memory" phenotype T cells and not the CD4+CD25+ T cell subset to be critical for the reduction in GVHD. Conclusions: These data demonstrate that LIP of T cells regulates acute GVHD severity in contrast to their ability to cause increased allograft rejection, autoimmunity, or anti-tumor immunity.
UR - http://www.scopus.com/inward/record.url?scp=33846341835&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33846341835&partnerID=8YFLogxK
U2 - 10.1016/j.exphem.2006.10.010
DO - 10.1016/j.exphem.2006.10.010
M3 - Article
C2 - 17258076
AN - SCOPUS:33846341835
VL - 35
SP - 274
EP - 286
JO - Experimental Hematology
JF - Experimental Hematology
SN - 0301-472X
IS - 2
ER -