Frequencies of donor-reactive helper T lymphocytes correlate with rejection of aortic valve allografts in rats.
OBJECTIVE
Human valve allografts are commonly used in cardiac surgery for congenital and acquired valve diseases. Particularly in the pediatric population, these allografts are prone to fail in the long term, and require replacement. In part, this failure may be due to immunological phenomena. The frequency of helper T lymphocytes (HTLf) measured in peripheral blood and spleen serves as a parameter for acute rejection in organ transplantation. The value of this parameter in valve transplantation was studied using the 'Rotterdam' implantation model in rats.


METHODS
HTLf were determined in peripheral blood and spleen at seven and 21 days after allogeneic (WAG-->DA) and syngeneic (DA-->DA) implantation of an aortic valved conduit. Valve competence was tested pre-implantation, at days 7 and 21 after implantation, and after explantation using a retrograde saline injection. Explanted valves were examined histologically.


RESULTS
At seven days after allogeneic valve transplantation, HTLf in spleen (median 71/10(6)), but not in peripheral blood (median 26/106) were significantly elevated. At 21 days after allogeneic transplantation, a significant increase in HTLf was seen in both peripheral blood (median 10(9)/10(6)) and spleen (median 92/10(6)). All five (100%) syngeneic grafts and five of seven (71%) allografts were competent at day 7. At day 21, all five syngeneic grafts (100%) and zero allografts (0%) remained competent (p = 0.01). Histologically, mononuclear cell infiltration into the allogeneic valve leaflets and in the vascular wall was observed at day 7. At day 21, valve leaflets appeared to be acellular and deformed. All syngeneic valve grafts retained normal morphology.


CONCLUSIONS
After aortic valve allografting in the rat, HTLf correlate with valve dysfunction and histopathological signs of rejection. Therefore, HTLf-analysis may be a useful tool in monitoring the cellular immune response as an indicator for early graft dysfunction due to rejection in clinical valve transplantation.
Dor
Frank J M F
FJ
Department of Internal Medicine, University Hospital Rotterdam-Dijkzigt, The Netherlands.
Oei
Frans B S
FB
Vaessen
Leonard M B
LM
Marquet
Richard L
RL
Bogers
Ad J J C
AJ
Weimar
Willem
W
D000818:Animals; D001021:Aortic Valve / Q000276:immunology* / Q000473:pathology / Q000637:transplantation*; D002470:Cell Survival / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006648:Histocompatibility / Q000276:immunology; D007121:Immunocompetence / Q000276:immunology; D008297:Male; D008955:Models, Cardiovascular; D051381:Rats; D011919:Rats, Inbred Strains; D016038:Skin Transplantation / Q000276:immunology; D013223:Statistics as Topic; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000473:pathology; D014019:Tissue Donors; D014157:Transcription Factors / Q000276:immunology; D014184:Transplantation, Homologous
D004268:DNA-Binding Proteins; C075814:FOXN2 protein, human; D051858:Forkhead Transcription Factors; D014157:Transcription Factors