Abstract
Background: Cotreatment with regulatory T cells (Treg) and conventional allogeneic bone marrow transplantation (BMT) successfully induced durable chimerism and tolerance to nonvascularized skin allografts without cytoreductive conditioning in mice. We sought to determine whether T reg treatment combined with vascularized BMT (VBMT) could create mixed chimerism and induce tolerance to vascularized composite allografts (VCAs) without cytoreductive conditioning in rats. Methods: Recipient Lewis rats treated (day 0) with or without naturally sorted Treg (3 × 106) from Lewis rat spleen and lymph nodes received costimulation blockade (anti-CD154 monoclonal antibody, days 0 and 1 and CTLA-4 immunoglobin, days 2, 4, and 6), rapamycin (days -1, 0, and 2), and concurrent transplantation of fully mismatched allogeneic donor VCAs (day 0) from the Brown Norway rat hindlimb containing VBMT. The mixed chimerism level was assessed monthly using flow cytometry. Survival of VCAs and occurrence of graft-versus-host disease were assessed clinically and histologically. Results: The combination of T reg and VBMT treatment led to long-term multilineage hematopoietic mixed chimerism (12-18%) and long-term donor-specific tolerance to VCAs (89% acceptance rate). Neither stable mixed chimerism nor VCA acceptance was observed in recipients without Treg treatment. Graft-versus-host disease did not occur in the VBMT recipients. Conclusions: Cotreatment with Treg and VBMT created stable mixed chimerism and induced long-term donor-specific tolerance to VCAs without requiring cytoreductive conditioning. This noncytoreductive Treg-VBMT protocol has potential for clinical application in VCAs.
| Original language | English |
|---|---|
| Pages (from-to) | 974-981 |
| Number of pages | 8 |
| Journal | Journal of Surgical Research |
| Volume | 178 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Dec 2012 |
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Keywords
- Graft-versus-host disease
- Mixed chimerism
- Regulatory T cells
- T
- Vascularized bone marrow transplantation
- Vascularized composite allograft
ASJC Scopus subject areas
- Surgery
Cite this
Combined treatment with regulatory T cells and vascularized bone marrow transplantation creates mixed chimerism and induces donor-specific tolerance to vascularized composite allografts without cytoreductive conditioning. / Lin, Jeng Yee; Tsai, Feng Chou; Wallace, Christopher Glenn; Huang, Wei Chao; Wei, Fu Chan; Liao, Shuen Kuei.
In: Journal of Surgical Research, Vol. 178, No. 2, 12.2012, p. 974-981.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Combined treatment with regulatory T cells and vascularized bone marrow transplantation creates mixed chimerism and induces donor-specific tolerance to vascularized composite allografts without cytoreductive conditioning
AU - Lin, Jeng Yee
AU - Tsai, Feng Chou
AU - Wallace, Christopher Glenn
AU - Huang, Wei Chao
AU - Wei, Fu Chan
AU - Liao, Shuen Kuei
PY - 2012/12
Y1 - 2012/12
N2 - Background: Cotreatment with regulatory T cells (Treg) and conventional allogeneic bone marrow transplantation (BMT) successfully induced durable chimerism and tolerance to nonvascularized skin allografts without cytoreductive conditioning in mice. We sought to determine whether T reg treatment combined with vascularized BMT (VBMT) could create mixed chimerism and induce tolerance to vascularized composite allografts (VCAs) without cytoreductive conditioning in rats. Methods: Recipient Lewis rats treated (day 0) with or without naturally sorted Treg (3 × 106) from Lewis rat spleen and lymph nodes received costimulation blockade (anti-CD154 monoclonal antibody, days 0 and 1 and CTLA-4 immunoglobin, days 2, 4, and 6), rapamycin (days -1, 0, and 2), and concurrent transplantation of fully mismatched allogeneic donor VCAs (day 0) from the Brown Norway rat hindlimb containing VBMT. The mixed chimerism level was assessed monthly using flow cytometry. Survival of VCAs and occurrence of graft-versus-host disease were assessed clinically and histologically. Results: The combination of T reg and VBMT treatment led to long-term multilineage hematopoietic mixed chimerism (12-18%) and long-term donor-specific tolerance to VCAs (89% acceptance rate). Neither stable mixed chimerism nor VCA acceptance was observed in recipients without Treg treatment. Graft-versus-host disease did not occur in the VBMT recipients. Conclusions: Cotreatment with Treg and VBMT created stable mixed chimerism and induced long-term donor-specific tolerance to VCAs without requiring cytoreductive conditioning. This noncytoreductive Treg-VBMT protocol has potential for clinical application in VCAs.
AB - Background: Cotreatment with regulatory T cells (Treg) and conventional allogeneic bone marrow transplantation (BMT) successfully induced durable chimerism and tolerance to nonvascularized skin allografts without cytoreductive conditioning in mice. We sought to determine whether T reg treatment combined with vascularized BMT (VBMT) could create mixed chimerism and induce tolerance to vascularized composite allografts (VCAs) without cytoreductive conditioning in rats. Methods: Recipient Lewis rats treated (day 0) with or without naturally sorted Treg (3 × 106) from Lewis rat spleen and lymph nodes received costimulation blockade (anti-CD154 monoclonal antibody, days 0 and 1 and CTLA-4 immunoglobin, days 2, 4, and 6), rapamycin (days -1, 0, and 2), and concurrent transplantation of fully mismatched allogeneic donor VCAs (day 0) from the Brown Norway rat hindlimb containing VBMT. The mixed chimerism level was assessed monthly using flow cytometry. Survival of VCAs and occurrence of graft-versus-host disease were assessed clinically and histologically. Results: The combination of T reg and VBMT treatment led to long-term multilineage hematopoietic mixed chimerism (12-18%) and long-term donor-specific tolerance to VCAs (89% acceptance rate). Neither stable mixed chimerism nor VCA acceptance was observed in recipients without Treg treatment. Graft-versus-host disease did not occur in the VBMT recipients. Conclusions: Cotreatment with Treg and VBMT created stable mixed chimerism and induced long-term donor-specific tolerance to VCAs without requiring cytoreductive conditioning. This noncytoreductive Treg-VBMT protocol has potential for clinical application in VCAs.
KW - Graft-versus-host disease
KW - Mixed chimerism
KW - Regulatory T cells
KW - T
KW - Vascularized bone marrow transplantation
KW - Vascularized composite allograft
UR - http://www.scopus.com/inward/record.url?scp=84869095117&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84869095117&partnerID=8YFLogxK
U2 - 10.1016/j.jss.2012.06.061
DO - 10.1016/j.jss.2012.06.061
M3 - Article
C2 - 22819314
AN - SCOPUS:84869095117
VL - 178
SP - 974
EP - 981
JO - Journal of Surgical Research
JF - Journal of Surgical Research
SN - 0022-4804
IS - 2
ER -