Genetics of the Blood Transfusion Effect on Heart Allografts in Rats

Soulillou, Jean Paul; Blandin, F.; Günther, Eberhard; Lemoine, V.

doi:10.1097/00007890-198407000-00015

Cited by 75 publications

(62 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Long-term survival of heart grafts was obtained by two DST of 1 mL heparinized LEW.1 W blood to LEW.1A recipients on pre-transplant days -14 and -7 [7]. Adoptive cell transfers were performed the day of the transplantation on an LEW.1A secondary naive recipient sublethally irradiated (4.5 Gy) 3 days before transplantation.…”

Section: Methodsmentioning

confidence: 99%

“…Long-term survival of heart grafts was obtained by two DST of 1 mL heparinized LEW.1 W blood to LEW.1A recipients on pre-transplant days -14 and -7 [7].…”

Section: Methodsmentioning

confidence: 99%

“…In adult rats, long-term survival of MHC-incompatible vascularized allografts (heart or kidney) can be obtained by priming the recipients with donor blood cells [7,8]. We and others have shown that inhibition of early allograft rejection by DST mostly affects helper T cell functions [9][10][11] and requires intact resident dendritic cells at the time of transplantation [12].…”

Section: Introductionmentioning

confidence: 99%

“…Donor-specific blood transfusion (DST) is a clinically and experimentally proven method to induce hyporesponsiveness and does not necessarily require additional immunotherapy [2][3][4][5][6]. However, the use of DST clinically has become less popular with the advent of calcineurin inhibitors and because a clear understanding of the mechanisms involved had remained elusive [4,6].In adult rats, long-term survival of MHC-incompatible vascularized allografts (heart or kidney) can be obtained by priming the recipients with donor blood cells [7,8]. We and others have shown that inhibition of early allograft rejection by DST mostly affects helper T cell functions [9][10][11] and requires intact resident dendritic cells at the time of transplantation [12].…”

mentioning

confidence: 99%

“…LEW.1 W or BN heart grafts were implanted heterotypically onto the LEW.1A recipient abdominal aorta and vena cava by using standard microsurgical techniques [55]. The graft was monitored by daily abdominal palpation and rejection was defined as complete cessation of heartbeat.Long-term survival of heart grafts was obtained by two DST of 1 mL heparinized LEW.1 W blood to LEW.1A recipients on pre-transplant days -14 and -7 [7]. Adoptive cell transfers were performed the day of the transplantation on an LEW.1A secondary naive recipient sublethally irradiated (4.5 Gy) 3 days before transplantation.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Development of CD25^– regulatory T cells following heart transplantation: Evidence for transfer of long‐term survival

et al. 2006

View full text Add to dashboard Cite

Donor-specific heart allograft acceptance can be induced in the MHC-mismatched LEW.1 W to LEW.1A rat by donor-specific transfusions. Whereas the induction phase of tolerance has been studied in detail, its maintenance remained poorly understood. Here, we performed a side-by-side comparison of CD25 + and CD25 -splenic T cells of 100-day tolerant rats. Administration of CD25 -T cells from tolerant rats to sublethally irradiated recipients transferred long-term graft survival. These CD25 -T cells displayed a decreased donor-specific response in the mixed lymphocyte reaction and presented suppressive activity. These CD25 -T cells accumulated IFN-c, IL-10 and Foxp3 transcripts. The in vitro suppressive activity of CD25 -T cells required both cell contact and soluble factors (IL-10 and IFN-c). The CD25 + T cells from tolerant rats did not show any modification of their regulatory properties. We show that splenic CD25 -T cells of tolerant rats contribute to the maintenance of tolerance following the transplantation. Our data show that regulatory T cells are not restricted to the CD4 + CD25 + T cell subset and provide new insights on the mechanisms of tolerance to allograft following donor cell priming. IntroductionInduction of specific tolerance for donor antigens (see [1] for review) is one of the most actively explored fields in transplantation immunology. Donor-specific blood transfusion (DST) is a clinically and experimentally proven method to induce hyporesponsiveness and does not necessarily require additional immunotherapy [2][3][4][5][6]. However, the use of DST clinically has become less popular with the advent of calcineurin inhibitors and because a clear understanding of the mechanisms involved had remained elusive [4,6].In adult rats, long-term survival of MHC-incompatible vascularized allografts (heart or kidney) can be obtained by priming the recipients with donor blood cells [7,8]. We and others have shown that inhibition of early allograft rejection by DST mostly affects helper T cell functions [9][10][11] and requires intact resident dendritic cells at the time of transplantation [12]. Early production of and differentiation of CD8 + clonal regulatory cells [14][15][16] are also involved. DST treatment results in a complex state where symptoms of chronic graft rejection coexist [17] with mechanisms controlling the host acute anti-donor immune response. Long-term recipients accept a donor-derived skin graft whereas a third-party graft is rejected [17]. Moreover, the spleen [18], and possibly the graft itself [19], * These authors contributed equally to this paper. ** These authors contributed equally to this paper. harbors donor-specific regulatory T cells able to protect naive recipients from allogeneic heart rejection. Therefore, the immunological status of allograft recipients following DST pre-conditioning provides another example of the differentiation of regulatory cells described in mice [20][21][22][23] or in rats [18,24] following different "tolerance" induction maneuvers (see [25] for review)...

show abstract

Section: Methodsmentioning

confidence: 99%

“…Long-term survival of heart grafts was obtained by two DST of 1 mL heparinized LEW.1 W blood to LEW.1A recipients on pre-transplant days -14 and -7 [7].…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Development of CD25^– regulatory T cells following heart transplantation: Evidence for transfer of long‐term survival

et al. 2006

View full text Add to dashboard Cite

show abstract

Recombinant IFN-γ abrogates allograft tolerance induced by donor-specific blood transfusion by restoring alloantibody production

et al. 1999

View full text Add to dashboard Cite

Donor-specific tolerance to heart allograft was induced in adult Lewis rats by pregraft donor-specific blood transfusion (DST). We previously showed that this tolerant state is characterized by a dramatic inhibition of T cell and macrophage activation. In addition, tolerant animals could not mount an efficient anti-donor humoral response whereas transfer of sera from rejecting animals triggered rejection in tolerant animals. This tolerance can be abrogated by daily post-graft administration of recombinant IFN-gamma (rIFN-gamma). To elucidate the mechanisms of action of rIFN-gamma, T cell, macrophage and B cell functions were assessed in allograft recipients. IFN-gamma did not restore the expression of Th1-related cytokine mRNA or the activated macrophage product inducible nitric oxide synthase in allografts. Importantly, rIFN-gamma treatment promptly restored the anti-donor humoral response in DST-treated recipients. We conclude that rIFN-gamma treatment in DST-treated allograft recipients cannot reverse the unresponsive state of Th1 cells and macrophages infiltrating the graft, but can provide B cell help for IgG alloantibody production which is lacking in these animals.

show abstract

Reassessment of the role of CD8+ T cells in the induction of allograft tolerance by donor-specific blood transfusion

et al. 1999

View full text Add to dashboard Cite

Donor-specific allograft tolerance can be induced in adult rats by pregraft donor-specific blood transfusion (DST). We have previously shown that DST elicits in recipients the expansion of a donor-specific CD8 + T cell clone displaying the V g 18-D g 1-J g 2.7 TCR rearrangement, which rapidly infiltrates allografts after transplantation, suggesting a regulatory function for this clone in DST-induced tolerance. In this study, recipients were pretreated before grafting, using an anti-CD8 monoclonal antibody to deplete CD8 + T cells. CD8 depletion before DST and transplantation abrogated allograft tolerance, and the CD8 + T cell clone was absent from allografts. These effects were not observed when CD8 depletion was performed after DST but before transplantation. We conclude that CD8 + T cells play a role in the induction of allograft tolerance by DST.

show abstract

Genetics of the Blood Transfusion Effect on Heart Allografts in Rats

Cited by 75 publications

References 0 publications

Development of CD25^– regulatory T cells following heart transplantation: Evidence for transfer of long‐term survival

Development of CD25^– regulatory T cells following heart transplantation: Evidence for transfer of long‐term survival

Recombinant IFN-γ abrogates allograft tolerance induced by donor-specific blood transfusion by restoring alloantibody production

Reassessment of the role of CD8+ T cells in the induction of allograft tolerance by donor-specific blood transfusion

Contact Info

Product

Resources

About

Genetics of the Blood Transfusion Effect on Heart Allografts in Rats

Cited by 75 publications

References 0 publications

Development of CD25– regulatory T cells following heart transplantation: Evidence for transfer of long‐term survival

Development of CD25– regulatory T cells following heart transplantation: Evidence for transfer of long‐term survival

Recombinant IFN-γ abrogates allograft tolerance induced by donor-specific blood transfusion by restoring alloantibody production

Reassessment of the role of CD8+ T cells in the induction of allograft tolerance by donor-specific blood transfusion

Contact Info

Product

Resources

About

Development of CD25^– regulatory T cells following heart transplantation: Evidence for transfer of long‐term survival

Development of CD25^– regulatory T cells following heart transplantation: Evidence for transfer of long‐term survival