Leh Chang

Abstract

Remarkable success has been achieved in the transplantation of allogeneic cardiac grafts into newborn infants at Loma Linda University Medical Center. The superior graft survival rate documented in these patients has not correlated with the degree of immunosuppression rendered, or the selection of genetically matched donors. However, the clinical success has correlated with the age of the recipient at the time of receiving a transplant. Patients receiving an allograft within the first few weeks of life are unique in that they seem to accept the alloantigens of their cardiac graft while responding aggressively to antigens in their environment. These observations have prompted a search for an explanation of what appears to be a unique state of immunologic privilege in these recipients.

This study was designed to explore matching the genetic material of the donor with the specific recipient, and the donor with the non-inherited maternal antigens to which the recipient was exposed during gestation. This was accomplished in several ways, including analysis of a) phenotypes of donor and recipient serum-defined class I and II major histocompatibility antigens, b) mismatched donor antigens relative to non-inherited maternal antigens, and c) recipient responses to lymphocyte-defined donor antigens in mixed lymphocyte cultures. When these analyses failed to explain an apparent state of immunologic privilege, immunomodulation of the neonatal immune response was attempted through manipulations of cell-mediated reactions in vitro that were thought to represent possible in vivo phenomena. Through mixed lymhocyte culture experiments, neonatal immune cells were exposed to alloantigens of unrelated individuals (representing organ donors) in the presence of specific maternal alloantigens. Significant immune suppression was observed when maternal cells were cocultured with neonatal cells during alloantigen recognition and processing. This immunomodulation was further augmented by preculturing the neonatal cells with maternal cells for a short period before exposure to the unrelated alloantigens. This data suggests that the non-inherited maternal antigens present on the cocultured maternal cells had down-regulated the neonatal response to unrelated alloantigens. It is possible that the neonatal cells were responding in a manner that had been "programmed" in utero for prevention of harmful reactivity toward maternal tissues.

LLU Discipline

Microbiology

Department

Microbiology

School

Graduate School

First Advisor

Sandra L. Nehlsen-Cannarella

Second Advisor

John E. Lewis

Third Advisor

Barry L. Taylor

Fourth Advisor

R. Bruce Wilcox

Degree Name

Master of Science (MS)

Degree Level

M.S.

Year Degree Awarded

1990

Date (Title Page)

6-1990

Language

English

Library of Congress/MESH Subject Headings

Immunity, Maternally-Acquired; Suppressor Factors, Immunologic; Heart Transplantation -- in infancy & childhood

Type

Thesis

Page Count

xi; 111

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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