Donor-specific hyporeactivity after liver transplantation : Prominent decreases in donor-specific cytotoxic T lymphocyte precursor frequencies independent of changes in helper T lymphocyte precursor frequencies or suppressor cell activity

The development of immunological donor-specific hyporeactivity may account for the low incidence of chronic rejection after clinical liver transplantation. We investigated whether hyporeactivity commonly develops after liver transplantation by analyzing precursor frequencies of donor-reactive cytoto...

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Published in:	Transplantation Vol. 66; no. 4; pp. 516 - 522
Main Authors:	DE BRAN, A, VAN DEN BERG, A. P, HEPKEMA, B. G, VAN DIJK, E, HAAGSMA, E. B, HAUW THE, T, SLOOFF, M. J. H, LEMS, S. P. M, DE LEIJ, L. F. M. H, PROP, J
Format:	Journal Article
Language:	English
Published:	Hagerstown, MD Lippincott 27-08-1998
Subjects:	Biological and medical sciences Humans Immune Tolerance Liver Transplantation - immunology Liver, biliary tract, pancreas, portal circulation, spleen Lymphocyte Count Medical sciences Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Surgery of the digestive system T-Lymphocytes, Cytotoxic - immunology T-Lymphocytes, Helper-Inducer - immunology Tissue Donors Transplantation Immunology Human Mixed lymphocyte reaction Immune response Liver Precursor cell Hepatic disease Helper cell Cytotoxicity Transplantation Homotransplantation Mechanism Specificity Donor Immune tolerance T-Lymphocyte Digestive diseases Adult Frequency Suppressive cell
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Summary:	The development of immunological donor-specific hyporeactivity may account for the low incidence of chronic rejection after clinical liver transplantation. We investigated whether hyporeactivity commonly develops after liver transplantation by analyzing precursor frequencies of donor-reactive cytotoxic (CTLp) and helper (HTLp) T lymphocytes and mixed lymphocyte culture (MLC) reactivity in liver allograft recipients. We further studied whether CTLp hyporeactivity correlated with changes in donor-specific HTLp frequencies or suppressor cell activity. CTLp and HTLp frequencies and MLC reactivity against donor and third-party spleen cells were determined in pre- and posttransplantation peripheral blood samples from 18 recipients with good graft function 2 years after transplantation. By mixing posttransplantation samples (with "putative" suppressor cell activity) with pretransplantation samples (in which normal CTL activity with no suppressor cell activity is expected), the presence of suppressor cell activity in peripheral blood was analyzed. Two years after transplantation, all but one (94%) of the recipients had developed CTLp hyporeactivity as evidenced by reduced donor-specific CTLp frequencies. The development of hyporeactivity was not specific for any particular underlying disease. The occurrence of HTL hyporeactivity, however, was less frequent: 38% and 20% of recipients were HTLp and MLC hyporeactive, respectively. Decreases in CTLp frequencies did not correlate with decreased donor-specific HTL function or suppressor cell activity in peripheral blood samples. Donor-specific CTLp hyporeactivity can develop in the majority of liver allograft recipients, irrespective of underlying disease. Donor-specific HTL hyporeactivity, however, occurs infrequently. A reduction in donor-specific CTLp frequencies was found to be independent of changes in donor-specific HTLp or suppressor cell activity, suggesting that other mechanisms (e.g., clonal deletion) are operative in the reduction of donor-specific CTLp after liver transplantation.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0041-1337 1534-6080
DOI:	10.1097/00007890-199808270-00017