The influence of concordant xenografts on the humoral and cell-mediated immune responses to subsequent allografts in primates

Robert E. Michler, A. S. Shah, S. Itescu, D. P. O'Hair, S. Tugulea, P. A. Kwiatkowski, Z. Liu, J. L. Platt, E. A. Rose, N. Suciu-Foca

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Abstract

The humoral and cell-mediated immune responses to subsequent allografts were determined in primate recipients after concordant xenotransplantation as a bridge to allotransplantation. Heterotopic heart transplants (n = 4) were performed from cynomolgus monkeys into ABH type-matched olive baboons followed 2 weeks later by allotransplantation from ABH type-matched baboon donors. Allografts were explanted at 8 weeks. All recipients underwent splenectomy at the time of xenotransplantation and received immunosuppression with cyclosporine, azathioprine, and methylprednisolone. Concordant xenotransplantation in these primates did not induce humoral or cell-mediated immune responses that jeopardized subsequent allografts. The degree of xenospecific immune reactivity, as determined by specific cytotoxicity of recipient T-cell lines derived from the xenograft and extent of histologic xenograft rejection, did not predict the severity of subsequent allograft rejection. In two of the four recipients, xenotransplantation induced an alloreactive humoral response against antigens expressed by the B cells of more than 50% of members from a panel of 12 unrelated baboons. In all recipients, priming with xenogeneic splenocytes in vitro induced an accelerated proliferative T-cell response to allogeneic lymphocytes from 16% of this panel. This study affirms the role of concordant xenografts as appropriate biologic bridges to human allotransplantation. However, our results suggest that xenoreactive baboon memory CD4 T cells may recognize major histocompatibility complex class II-like structures shared between the xenogeneic and allogeneic targets. The potential allorecognition induced by a xenograft may affect the process of subsequent allograft donor selection.

Original languageEnglish (US)
Pages (from-to)1002-1009
Number of pages8
JournalJournal of Thoracic and Cardiovascular Surgery
Volume112
Issue number4
DOIs
StatePublished - 1996
Externally publishedYes

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Heterologous Transplantation
Heterografts
Primates
Allografts
Papio
T-Lymphocytes
Papio anubis
Donor Selection
Macaca fascicularis
Methylprednisolone
Azathioprine
Splenectomy
Major Histocompatibility Complex
Immunosuppression
Cyclosporine
B-Lymphocytes
Lymphocytes
Transplants
Antigens
Cell Line

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

The influence of concordant xenografts on the humoral and cell-mediated immune responses to subsequent allografts in primates. / Michler, Robert E.; Shah, A. S.; Itescu, S.; O'Hair, D. P.; Tugulea, S.; Kwiatkowski, P. A.; Liu, Z.; Platt, J. L.; Rose, E. A.; Suciu-Foca, N.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 112, No. 4, 1996, p. 1002-1009.

Research output: Contribution to journalArticle

Michler, RE, Shah, AS, Itescu, S, O'Hair, DP, Tugulea, S, Kwiatkowski, PA, Liu, Z, Platt, JL, Rose, EA & Suciu-Foca, N 1996, 'The influence of concordant xenografts on the humoral and cell-mediated immune responses to subsequent allografts in primates', Journal of Thoracic and Cardiovascular Surgery, vol. 112, no. 4, pp. 1002-1009. https://doi.org/10.1016/S0022-5223(96)70101-0
Michler, Robert E. ; Shah, A. S. ; Itescu, S. ; O'Hair, D. P. ; Tugulea, S. ; Kwiatkowski, P. A. ; Liu, Z. ; Platt, J. L. ; Rose, E. A. ; Suciu-Foca, N. / The influence of concordant xenografts on the humoral and cell-mediated immune responses to subsequent allografts in primates. In: Journal of Thoracic and Cardiovascular Surgery. 1996 ; Vol. 112, No. 4. pp. 1002-1009.
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AU - Kwiatkowski, P. A.

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