Perinatal induction of immunotolerance to cardiac and pulmonary allografts

D. D. Yuh, K. L. Gandy, B. A. Reitz, G. Hoyt, R. C. Robbins

Research output: Contribution to journalArticle

Abstract

Objectives: Tolerance appears to be more easily induced in the fetus before full immunocompetence is established, but elucidation of this process is needed. A model of perinatal tolerance induction to neonatal skin allografts followed by cardiac and pulmonary allografts is described. Methods: Sixty Lewis (RT1(I)) rat fetuses were inoculated intraperitoneally at 18 days' gestation with 1 x 107 ACI (RT1a) rat fetal liver cells (group I); 20 Lewis fetuses were inoculated with 2 x 107 ACI fetal liver cells (group II). Control groups consisted of Lewis fetuses inoculated with saline solution (n = 25, group III) and fetuses that were not inoculated (n = 25, group IV). Twenty-five of the 50 surviving group I rats received ACI skin (2 test). A 100-fold reduction of precursor cytotoxic T lymphocytes and significant splenocyte and bone marrow chimerism in tolerant versus nontolerant rats were noted (p = 0.0001, Student's t test). Conclusions: Using donor-strain fetal liver cells and neonatal skin grafts, we achieved higher frequencies of tolerance to solid organ grafts in adulthood with lower cell inocula and abortion rates than previously described. Chimerism and depressed precursor cytotoxic T lymphocyte frequencies in tolerant recipients suggest that hematopoietic stem cell engraftment and clonal deletion/anergy are involved in induction of perinatal tolerance.

Original languageEnglish (US)
Pages (from-to)64-75
Number of pages12
JournalJournal of Thoracic and Cardiovascular Surgery
Volume114
Issue number1
DOIs
StatePublished - 1997
Externally publishedYes

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Allografts
Fetus
Lung
Inbred ACI Rats
Chimerism
Cytotoxic T-Lymphocytes
Liver
Clonal Anergy
Clonal Deletion
Transplants
Immunocompetence
Skin
Induced Abortion
Hematopoietic Stem Cells
Skin Tests
Sodium Chloride
Bone Marrow
Tissue Donors
Students
Pregnancy

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Perinatal induction of immunotolerance to cardiac and pulmonary allografts. / Yuh, D. D.; Gandy, K. L.; Reitz, B. A.; Hoyt, G.; Robbins, R. C.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 114, No. 1, 1997, p. 64-75.

Research output: Contribution to journalArticle

Yuh, D. D. ; Gandy, K. L. ; Reitz, B. A. ; Hoyt, G. ; Robbins, R. C. / Perinatal induction of immunotolerance to cardiac and pulmonary allografts. In: Journal of Thoracic and Cardiovascular Surgery. 1997 ; Vol. 114, No. 1. pp. 64-75.
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