Maternal Immunomodulation of Neonatal Alloantigen Response

<p>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.</p> <p>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.</p>

Name thesis:degree_name

Master of Science (MS)

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Microbiology

Year

1990

Author dc:creator

• Chang, Leh

Contributors dc:contributor

• Sandra L. Nehlsen-Cannarella
• John E. Lewis
• Barry L. Taylor
• R. Bruce Wilcox

• Biochemistry
• Biological Phenomena, Cell Phenomena, and Immunity
• Genetic Phenomena
• Medical Genetics
• Medical Immunology
• Microbiology
• Immunity, Maternally-Acquired; Suppressor Factors, Immunologic; Heart Transplantation -- in infancy & childhood

Statement dc: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.

Language dc:language

English

Repository record dc:identifier

https://scholarsrepository.llu.edu/etd/1409

OAI identifier oai:identifier

oai:scholarsrepository.llu.edu:etd-2181