Abstract
CD26 (DPP4) is a T cell costimulatory molecule as well as T cell activation marker, and CD26+ T cells are accumulated in inflamed tissues, such as rheumatoid synovitis and autoimmune thyroiditis. In the present study, we found accumulation of CD26+ T cells in graft-versus-host disease (GVHD) target organs. To expand our in vitro findings to an in vivo system, we examined CD26-dependent organ injury in a xenogeneic GVHD (x-GVHD) murine model. Following intraperitoneal injection of human peripheral blood mononuclear cells into non-obese diabetic severe combined immunodeficiency/γc -/- mice (hu-PBL-NOG mice), the mice exhibited the onset of GVHD symptoms associated with the presence of CD26high human lymphocytes in the peripheral blood and GVHD target tissues. Administration of humanized anti-human CD26 monoclonal antibody (mAb) decreased x-GVHD severity and prolonged survival in hu-PBL-NOG mice without loss of engraftment of human T cells, while increasing doses of CTLA4- immunoglobulin fusion protein diminished engraftment of human lymphocytes. Importantly, anti-CD26 mAb treatment preserved the graft-versus-leukaemia effects in studies using cotransplantation of P815 murine leukaemic cells. In addition, CD26+ lymphocytes infiltrated the GVHD patients' target tissues. Altogether, our data indicate a role for CD26 in the regulation of GVHD and point to CD26 as a novel target for therapeutic intervention in this disease.
| Original language | English |
|---|---|
| Pages (from-to) | 263-277 |
| Number of pages | 15 |
| Journal | British Journal of Haematology |
| Volume | 162 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2013 Jul |
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Keywords
- CD26 (DPP4)
- Graft-versus-host disease
- Haematopoietic stem cell transplantation
- T cell costimulation
ASJC Scopus subject areas
- Hematology
Cite this
Prevention of acute graft-versus-host disease by humanized anti-CD26 monoclonal antibody. / Hatano, Ryo; Ohnuma, Kei; Yamamoto, Junpei; Dang, Nam H.; Yamada, Taketo; Morimoto, Chikao.
In: British Journal of Haematology, Vol. 162, No. 2, 07.2013, p. 263-277.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Prevention of acute graft-versus-host disease by humanized anti-CD26 monoclonal antibody
AU - Hatano, Ryo
AU - Ohnuma, Kei
AU - Yamamoto, Junpei
AU - Dang, Nam H.
AU - Yamada, Taketo
AU - Morimoto, Chikao
PY - 2013/7
Y1 - 2013/7
N2 - CD26 (DPP4) is a T cell costimulatory molecule as well as T cell activation marker, and CD26+ T cells are accumulated in inflamed tissues, such as rheumatoid synovitis and autoimmune thyroiditis. In the present study, we found accumulation of CD26+ T cells in graft-versus-host disease (GVHD) target organs. To expand our in vitro findings to an in vivo system, we examined CD26-dependent organ injury in a xenogeneic GVHD (x-GVHD) murine model. Following intraperitoneal injection of human peripheral blood mononuclear cells into non-obese diabetic severe combined immunodeficiency/γc -/- mice (hu-PBL-NOG mice), the mice exhibited the onset of GVHD symptoms associated with the presence of CD26high human lymphocytes in the peripheral blood and GVHD target tissues. Administration of humanized anti-human CD26 monoclonal antibody (mAb) decreased x-GVHD severity and prolonged survival in hu-PBL-NOG mice without loss of engraftment of human T cells, while increasing doses of CTLA4- immunoglobulin fusion protein diminished engraftment of human lymphocytes. Importantly, anti-CD26 mAb treatment preserved the graft-versus-leukaemia effects in studies using cotransplantation of P815 murine leukaemic cells. In addition, CD26+ lymphocytes infiltrated the GVHD patients' target tissues. Altogether, our data indicate a role for CD26 in the regulation of GVHD and point to CD26 as a novel target for therapeutic intervention in this disease.
AB - CD26 (DPP4) is a T cell costimulatory molecule as well as T cell activation marker, and CD26+ T cells are accumulated in inflamed tissues, such as rheumatoid synovitis and autoimmune thyroiditis. In the present study, we found accumulation of CD26+ T cells in graft-versus-host disease (GVHD) target organs. To expand our in vitro findings to an in vivo system, we examined CD26-dependent organ injury in a xenogeneic GVHD (x-GVHD) murine model. Following intraperitoneal injection of human peripheral blood mononuclear cells into non-obese diabetic severe combined immunodeficiency/γc -/- mice (hu-PBL-NOG mice), the mice exhibited the onset of GVHD symptoms associated with the presence of CD26high human lymphocytes in the peripheral blood and GVHD target tissues. Administration of humanized anti-human CD26 monoclonal antibody (mAb) decreased x-GVHD severity and prolonged survival in hu-PBL-NOG mice without loss of engraftment of human T cells, while increasing doses of CTLA4- immunoglobulin fusion protein diminished engraftment of human lymphocytes. Importantly, anti-CD26 mAb treatment preserved the graft-versus-leukaemia effects in studies using cotransplantation of P815 murine leukaemic cells. In addition, CD26+ lymphocytes infiltrated the GVHD patients' target tissues. Altogether, our data indicate a role for CD26 in the regulation of GVHD and point to CD26 as a novel target for therapeutic intervention in this disease.
KW - CD26 (DPP4)
KW - Graft-versus-host disease
KW - Haematopoietic stem cell transplantation
KW - T cell costimulation
UR - http://www.scopus.com/inward/record.url?scp=84879841516&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84879841516&partnerID=8YFLogxK
U2 - 10.1111/bjh.12378
DO - 10.1111/bjh.12378
M3 - Article
C2 - 23692598
AN - SCOPUS:84879841516
VL - 162
SP - 263
EP - 277
JO - British Journal of Haematology
JF - British Journal of Haematology
SN - 0007-1048
IS - 2
ER -