New strategies for early diagnosis of heart allograft rejection

Sorina Tugulea, Rodica Ciubotariu, Adriana I. Colovai, Zhuoru Liu, Silviu Itescu, Larry L. Schulman, Peter E. Fisher, Mark A. Hardy, Eric A. Rose, Robert E. Michler, Raffaello Cortesini, Nicole Suciu-Foca

Research output: Contribution to journalArticle

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Abstract

Background. Allograft rejection is mediated by T cells that recognize allogeneic major histocompatibility complex (MHC) molecules via the direct and indirect pathway. The direct pathway involves T cells that react against MHC/peptide complexes expressed on the surface of donor antigen-presenting cells (APCs). In contrast, T cells involved in the indirect pathway recognize peptides derived from processing and presentation of allogeneic MHC molecules by self (recipient) APCs. To explore the relative contribution of these two pathways to rejection, we have evaluated the response of peripheral blood T cells from 50 heart transplant recipients against donor APCs (direct recognition) and against self APCs pulsed with synthetic peptides corresponding to the hypervariable region of the mismatched HLA-DR antigens of the donor (indirect recognition). Methods. T cell reactivity against donor APCs was quantitated by measuring the expression of CD69 on allostimulated CD3+LDA1+ cells. Reactivity to synthetic allopeptides was determined in limited dilution assays. Results. Serial studies of the kinetics of direct and indirect recognition showed that both pathways contribute to early acute rejection episodes. Primary rejection was accompanied invariably by indirect recognition of a dominant allopeptide. Intermolecular spreading of T cell epitopes was observed during recurrent rejections. Enhanced recognition of donor alloantigens via the direct pathway was found predominantly during early rejection episodes. A single form of allorecognition was shown to occur in some rejection episodes. Conclusions. Monitoring of the direct and indirect pathway of allorecognition provides a reliable method for prediction and differential diagnosis of acute rejection of heart allografts.

Original languageEnglish (US)
Pages (from-to)842-847
Number of pages6
JournalTransplantation
Volume64
Issue number6
DOIs
StatePublished - Sep 27 1997
Externally publishedYes

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Antigen-Presenting Cells
Allografts
Early Diagnosis
T-Lymphocytes
Major Histocompatibility Complex
Tissue Donors
Autoantigens
Peptides
T-Lymphocyte Epitopes
Isoantigens
HLA-DR Antigens
Surface Antigens
Blood Cells
Differential Diagnosis

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Tugulea, S., Ciubotariu, R., Colovai, A. I., Liu, Z., Itescu, S., Schulman, L. L., ... Suciu-Foca, N. (1997). New strategies for early diagnosis of heart allograft rejection. Transplantation, 64(6), 842-847. https://doi.org/10.1097/00007890-199709270-00009

New strategies for early diagnosis of heart allograft rejection. / Tugulea, Sorina; Ciubotariu, Rodica; Colovai, Adriana I.; Liu, Zhuoru; Itescu, Silviu; Schulman, Larry L.; Fisher, Peter E.; Hardy, Mark A.; Rose, Eric A.; Michler, Robert E.; Cortesini, Raffaello; Suciu-Foca, Nicole.

In: Transplantation, Vol. 64, No. 6, 27.09.1997, p. 842-847.

Research output: Contribution to journalArticle

Tugulea, S, Ciubotariu, R, Colovai, AI, Liu, Z, Itescu, S, Schulman, LL, Fisher, PE, Hardy, MA, Rose, EA, Michler, RE, Cortesini, R & Suciu-Foca, N 1997, 'New strategies for early diagnosis of heart allograft rejection', Transplantation, vol. 64, no. 6, pp. 842-847. https://doi.org/10.1097/00007890-199709270-00009
Tugulea S, Ciubotariu R, Colovai AI, Liu Z, Itescu S, Schulman LL et al. New strategies for early diagnosis of heart allograft rejection. Transplantation. 1997 Sep 27;64(6):842-847. https://doi.org/10.1097/00007890-199709270-00009
Tugulea, Sorina ; Ciubotariu, Rodica ; Colovai, Adriana I. ; Liu, Zhuoru ; Itescu, Silviu ; Schulman, Larry L. ; Fisher, Peter E. ; Hardy, Mark A. ; Rose, Eric A. ; Michler, Robert E. ; Cortesini, Raffaello ; Suciu-Foca, Nicole. / New strategies for early diagnosis of heart allograft rejection. In: Transplantation. 1997 ; Vol. 64, No. 6. pp. 842-847.
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abstract = "Background. Allograft rejection is mediated by T cells that recognize allogeneic major histocompatibility complex (MHC) molecules via the direct and indirect pathway. The direct pathway involves T cells that react against MHC/peptide complexes expressed on the surface of donor antigen-presenting cells (APCs). In contrast, T cells involved in the indirect pathway recognize peptides derived from processing and presentation of allogeneic MHC molecules by self (recipient) APCs. To explore the relative contribution of these two pathways to rejection, we have evaluated the response of peripheral blood T cells from 50 heart transplant recipients against donor APCs (direct recognition) and against self APCs pulsed with synthetic peptides corresponding to the hypervariable region of the mismatched HLA-DR antigens of the donor (indirect recognition). Methods. T cell reactivity against donor APCs was quantitated by measuring the expression of CD69 on allostimulated CD3+LDA1+ cells. Reactivity to synthetic allopeptides was determined in limited dilution assays. Results. Serial studies of the kinetics of direct and indirect recognition showed that both pathways contribute to early acute rejection episodes. Primary rejection was accompanied invariably by indirect recognition of a dominant allopeptide. Intermolecular spreading of T cell epitopes was observed during recurrent rejections. Enhanced recognition of donor alloantigens via the direct pathway was found predominantly during early rejection episodes. A single form of allorecognition was shown to occur in some rejection episodes. Conclusions. Monitoring of the direct and indirect pathway of allorecognition provides a reliable method for prediction and differential diagnosis of acute rejection of heart allografts.",
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AU - Ciubotariu, Rodica

AU - Colovai, Adriana I.

AU - Liu, Zhuoru

AU - Itescu, Silviu

AU - Schulman, Larry L.

AU - Fisher, Peter E.

AU - Hardy, Mark A.

AU - Rose, Eric A.

AU - Michler, Robert E.

AU - Cortesini, Raffaello

AU - Suciu-Foca, Nicole

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N2 - Background. Allograft rejection is mediated by T cells that recognize allogeneic major histocompatibility complex (MHC) molecules via the direct and indirect pathway. The direct pathway involves T cells that react against MHC/peptide complexes expressed on the surface of donor antigen-presenting cells (APCs). In contrast, T cells involved in the indirect pathway recognize peptides derived from processing and presentation of allogeneic MHC molecules by self (recipient) APCs. To explore the relative contribution of these two pathways to rejection, we have evaluated the response of peripheral blood T cells from 50 heart transplant recipients against donor APCs (direct recognition) and against self APCs pulsed with synthetic peptides corresponding to the hypervariable region of the mismatched HLA-DR antigens of the donor (indirect recognition). Methods. T cell reactivity against donor APCs was quantitated by measuring the expression of CD69 on allostimulated CD3+LDA1+ cells. Reactivity to synthetic allopeptides was determined in limited dilution assays. Results. Serial studies of the kinetics of direct and indirect recognition showed that both pathways contribute to early acute rejection episodes. Primary rejection was accompanied invariably by indirect recognition of a dominant allopeptide. Intermolecular spreading of T cell epitopes was observed during recurrent rejections. Enhanced recognition of donor alloantigens via the direct pathway was found predominantly during early rejection episodes. A single form of allorecognition was shown to occur in some rejection episodes. Conclusions. Monitoring of the direct and indirect pathway of allorecognition provides a reliable method for prediction and differential diagnosis of acute rejection of heart allografts.

AB - Background. Allograft rejection is mediated by T cells that recognize allogeneic major histocompatibility complex (MHC) molecules via the direct and indirect pathway. The direct pathway involves T cells that react against MHC/peptide complexes expressed on the surface of donor antigen-presenting cells (APCs). In contrast, T cells involved in the indirect pathway recognize peptides derived from processing and presentation of allogeneic MHC molecules by self (recipient) APCs. To explore the relative contribution of these two pathways to rejection, we have evaluated the response of peripheral blood T cells from 50 heart transplant recipients against donor APCs (direct recognition) and against self APCs pulsed with synthetic peptides corresponding to the hypervariable region of the mismatched HLA-DR antigens of the donor (indirect recognition). Methods. T cell reactivity against donor APCs was quantitated by measuring the expression of CD69 on allostimulated CD3+LDA1+ cells. Reactivity to synthetic allopeptides was determined in limited dilution assays. Results. Serial studies of the kinetics of direct and indirect recognition showed that both pathways contribute to early acute rejection episodes. Primary rejection was accompanied invariably by indirect recognition of a dominant allopeptide. Intermolecular spreading of T cell epitopes was observed during recurrent rejections. Enhanced recognition of donor alloantigens via the direct pathway was found predominantly during early rejection episodes. A single form of allorecognition was shown to occur in some rejection episodes. Conclusions. Monitoring of the direct and indirect pathway of allorecognition provides a reliable method for prediction and differential diagnosis of acute rejection of heart allografts.

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