Analysis of cell-mediated lympholysis in long-term liver allograft recipients indicated that there was a donor-specific unresponsiveness that could not be reversed by the addition of rIL-2 and/or mixed lymphocyte culture supernatant or by nonspecific stimulation of the cultures with PHA. Stimulation of recipient cells with semisyngeneic cells having both donor and third-party HLA antigens failed to reveal the presence of cytotoxic T cells (CTL) specific to the donor, whereas the CTL response to third-party antigens remained normal. Removal of B lymphocytes from the responding cell population did not influence the responses. Furthermore, limiting dilution analysis showed that the liver transplant recipients did not have detectable levels of CTL precursors (CTLp) reactive to the donor antigens, whereas their CTLp to third-party antigens remained normal. Donor-specific CTLp were present before and during the early post-transplant period; these cells were eliminated from the peripheral circulation by 10 mo after transplantation. Taken together, these results indicate that there is a deletion of CTLp specific to donor MHC antigens in the peripheral circulation of long-term liver allograft recipients that may account in part for the success of liver transplantation across MHC barriers.
J M Mathew, J W Marsh, B Susskind, T Mohanakumar
Title and authors | Publication | Year |
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Involvement of circulating soluble HLA-G after liver transplantation in the low immunogenicity of hepatic allograft.
Le Floc'h B, Costet N, Vu N, Bernabeu-Gentey P, Pronier C, Houssel-Debry P, Boudjéma K, Renac V, Samson M, Amiot L |
PloS one | 2023 |
Cellular and functional biomarkers of clinical transplant tolerance
JM Mathew, MJ Ansari, L Gallon, JR Leventhal |
Human Immunology | 2018 |
Immune "tolerance profiles" in donor bone marrow infused kidney transplant patients using multiple ex vivo functional assays
JM Mathew, G Ciancio, GW Burke, RO Garcia-Morales, A Rosen, E Wang, CI Gomez, BB Blomberg, L Fuller, V Esquenazi, C Ricordi, J Miller |
Human Immunology | 2010 |
Deficient TNF-α and IFN-γ Production Correlates With Nondetectable Donor-Specific Cytotoxicity After Clinical Kidney Transplantation
NM van Besouw, R Kuiper, BJ van der Mast, J de Wetering, CC Baan, W Weimar |
Transplantation | 2009 |
Serial Assessment of Immune Status by Circulating CD8+ Effector T Cell Frequencies for Posttransplant Infectious Complications
S Uemoto, K Ozawa, H Egawa, Y Takada, H Sato, S Teramukai, M Kasahara, K Ogawa, M Ono, K Takai, M Fukushima, K Inaba, K Tanaka |
Clinical and Developmental Immunology | 2008 |
Calcineurin Inhibitor Withdrawal in Stable Kidney Transplant Patients Decreases the Donor-Specific Cytotoxic T Lymphocyte Precursor Frequency
BJ van der Mast, J Rischen-Vos, P Kuiper, LM Vaessen, NM van Besouw, W Weimar |
Transplantation | 2005 |
Early biological and immune response to semi-identical liver or kidney allograft in miniature swine
M Otsuka, S Ambiru, K Uryuhara, P Herman, S Talpe, JP Dehoux, F Jamar, P Gianello |
Transplant International | 2005 |
THYMECTOMY IMPAIRS BUT DOES NOT UNIFORMLY ABROGATE LONG-TERM ACCEPTANCE OF SEMI-IDENTICAL LIVER ALLOGRAFT IN INBRED MINIATURE SWINE TEMPORARILY TREATED WITH FK506
K Uryuhara, S Ambiru, JP Dehoux, F Oike, S Talpe, P Gianello |
Transplantation | 2004 |
DEMONSTRATION THAT DONOR-SPECIFIC NONRESPONSIVENESS IN HUMAN LIVER ALLOGRAFT RECIPIENTS IS BOTH RARE AND TRANSIENT
M Hathaway, DH Adams |
Transplantation | 2004 |
Human donor bone marrow cells induce in vitro “suppressor T cells” that functionally suppress autologous B cells
MR Carreno, L Fuller, JM Mathew, G Ciancio, GW Burke, V Esquenazi, C Ricordi, AG Tzakis, J Miller |
Human Immunology | 2003 |
Hepatic expression of IL-15 mRNA is associated with liver graft acceptance
S Cookson, DG Doherty, S Todryk, P Gibbs, B Portmann, J O'Grady, M Rela, N Heaton, S Norris |
Transplant Immunology | 2003 |
A novel micro-cell-mediated lympholytic assay for the evaluation of regulatory cells in human alloreactive CTL responses
JM Mathew, B Blomberg, L Fuller, GW Burke, G Ciancio, N Kenyon, C Ricordi, AG Tzakis, V Esquenazi, J Miller |
Journal of Immunological Methods | 2003 |
Lymphocyte apoptosis and cell replacement in human liver allografts:
AD Clouston, JR Jonsson, GA Balderson, J Fawcett, SV Lynch, A Kelso, EE Powell |
Transplantation | 2002 |
RAPID DECREASES IN DONOR-SPECIFIC CYTOTOXIC T LYMPHOCYTE PRECURSOR FREQUENCIES AND GRAFT OUTCOME AFTER LIVER AND LUNG TRANSPLANTATION 1:
A de Haan, AP van den Berg, W van der Bij, BG Hepkema, EB Dijk, I van der Gun, SP Lems, MJ Slooff, EB Haagsma, LF de Leij, J Prop |
Transplantation | 2001 |
HUMAN LIVER ALLOGRAFT ACCEPTANCE AND THE ???TOLERANCE ASSAY???: IN VITRO ANTI-DONOR T CELL ASSAYS SHOW HYPOREACTIVITY TO DONOR CELLS, BUT UNLIKE DTH, FAIL TO DETECT LINKED SUPPRESSION1:
F Geissler, E Jankowska-Gan, LD DeVito-Haynes, T Rhein, M Kalayoglu, HW Sollinger, WJ Burlingham |
Transplantation | 2001 |
Cytomegalovirus immune globulin intravenous (human) administration modulates immune response to alloantigens in sensitized renal transplant candidates
KS Sivasai, T Mohanakumar, D Phelan, S Martin, ME Anstey, DC Brennan |
Clinical & Experimental Immunology | 2000 |
LIVER TRANSPLANT RECIPIENT SERA DERIVED SOLUBLE HLA MEDIATES ALLELE SPECIFIC CTL APOPTOSIS:
MA Smith, B Naziruddin, NJ Poindexter, AE Haynes, T Howard, T Mohanakumar |
Transplantation | 2000 |
T helper frequencies in peripheral blood reflect donor-directed reactivity in the graft after clinical heart transplantation
LM Vaessen, CR Daane, AP Maat, AH Balk, FH Claas, W Weimar |
Clinical & Experimental Immunology | 1999 |
Analysis of post-transplant immune status in recipients of liver/bone marrow allografts
MA Chatzipetrou, JM Mathew, NS Kenyon, V Esquenazi, J Miller, C Ricordi, AG Tzakis |
Human Immunology | 1999 |
Tolerance after liver transplantation: does it exist and can immunosuppression be withdrawn?
SM Riordan, R Williams |
Journal of Hepatology | 1999 |
Detection and characterization of HLA class I molecules in the supernatant of an hepatocarcinoma cell line and of EBV-transformed B cell lines
G Datema, A Mulder, FH Claas, PJ van Elsen |
Human Immunology | 1999 |
IN VITRO IMMUNOGENICITY OF CADAVER DONOR BONE MARROW CELLS USED FOR THE INDUCTION OF ALLOGRAFT ACCEPTANCE IN CLINICAL TRANSPLANTATION1:
JM Mathew, M Carreno, L Fuller, C Ricordi, N Kenyon, AG Tzakis, J Miller, V Esquenazi |
Transplantation | 1999 |
Donor-specific CTL frequencies in peripheral blood in relation to graft vascular disease after clinical heart transplantation
NM Besouw, CR Daane, P Kuiper, T Gelder, B Mochtar, AH Balk, LM Vaessen, W Weimar |
Transplant International | 1998 |
Donor-specific immunological non-responsiveness after liver transplantation
AP Berg, A Haan, BG Hepkema, E Dijk, E Twuyver, IJ Klompmaker, LH Leij, LP Waal, MJ Slooff, TH The |
Transplant International | 1998 |
Mutual tolerance after liver and not after heart transplantation? Evaluation of patient-anti-donor and donor-anti-patient responses by mixed lymphocyte culture
B van der Mast, NM van Besouw, BG Hepkema, W Weimar, AP van de Berg, MJ Slooff, FH Claas |
Transplant Immunology | 1998 |
Kinetics of circulating cytotoxic T lymphocyte precursors that have a high avidity for donor antigens: correlation with the rejection status of the human cardiac allograft
NE van Emmerik, LM Vaessen, CJ Knoop, CR Daane, AH Balk, B Mochtar, FH Claas, W Weimar |
Transplant Immunology | 1998 |
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 Activity1
A de Haan, AP van den Berg, BG Hepkema, E van Dijk, EB Haagsma, TH The, MJ Slooff, SP Lems, LF de Leij, J Prop |
Transplantation | 1998 |
Soluble Human Leukocyte Antigens, Interleukin-6, and Interferon-γ During Pregnancy
GP Russwurm, AM Mackler, OR Fagoaga, WS Brown, EP Sakala, SM Yellon, SL Nehlsen-Cannarella |
American Journal of Reproductive Immunology | 1997 |
Clinical significance of selective decline of donor-reactive IL-2-producing T lymphocytes after renal transplantation
AI Beik, RM Higgins, FT Lam, AG Morris |
Transplant Immunology | 1997 |
MODULATORY EFFECTS OF HUMAN DONOR BONE MARROW CELLS ON ALLOGENEIC CELLULAR IMMUNE RESPONSES1:
JM Mathew, M Carreno, L Fuller, C Ricordi, A Tzakis, V Esquenazi, J Miller |
Transplantation | 1997 |
Enumeration of human alloreactive helper T lymphocyte precursor frequencies by limiting dilution analysis of interleukin-2 production
NT Young, DL Roelen, MJ Dallman, KJ Wood, PJ Morris, KI Welsh |
Journal of Immunological Methods | 1996 |
Cytolytic effector mechanisms of human CD4+ cytotoxic T lymphocytes
B Susskind, MD Shornick, MR Iannotti, B Duffy, PM Tanden, JP Siegel, T Mohanakumar |
Human Immunology | 1996 |
Indirect allorecognition of HLA class I peptides by CD4+ cytolytic T lymphocytes
B Susskind, MR Iannotti, MD Shornick, NS Steward, J Gorka, T Mohanakumar |
Human Immunology | 1996 |
COMPARISON OF T CELL RESPONSES IN PATIENTS WITH A LONG-TERM SURVIVING RENAL ALLOGRAFT VERSUS A LONG-TERM SURVIVING LIVER ALLOGRAFT: It's a Different World
E van Twuyver, J de Hoop, RJ ten Berge, JM Wilmink, SP Lems, AP van de Berg, MJ Slooff, LP de Waal |
Transplantation | 1996 |
DELAYED-TYPE HYPERSENSITIVITY-LIKE MECHANISMS DOMINATE LATE ACUTE REJECTION EPISODES IN RENAL ALLOGRAFT RECIPIENTS1,2:
S Ode-Hakim, WD Dcke, F Kern, F Emmrich, HD Volk, P Reinke |
Transplantation | 1996 |
BIOCHEMICAL AND IMMUNOLOGICAL EVALUATION OF DONOR-SPECIFIC SOLUBLE HLA IN THE CIRCULATION OF LIVER TRANSPLANT RECIPIENTS1:
JM Mathew, S Shenoy, D Phelan, J Lowell, T Howard, T Mohanakumar |
Transplantation | 1996 |
Transplant-associated autoimmune mechanisms in human hepatitis C virus infection
K Zucker, D Roth, R Cirocco, J Mathew, M Carreno, L Fuller, T Karatzas, Y Jin, G Burke, J Nery, M Webb, A Tzakis, V Esquenazi, J Miller |
Journal of Clinical Immunology | 1996 |
Posttransplant donor antigen-specific hyporeactivity in human transplantation
NL Reinsmoen |
Transplantation Reviews | 1995 |
A sanguine outlook: The role of donor-specific transfusion in renal transplantation and tolerance
CB Anderson, DC Brennan |
Transplantation Reviews | 1995 |
Frequency of Hypoxanthine Guanine Phosphoribosyltransferase ( HPRT− ) T Cells in the Peripheral Blood of Cardiac Transplant Recipients: A Noninvasive Technique for the Diagnosis of Allograft Rejection
AA Ansari, A Mayne, JB Sundstrom, MB Gravanis, K Kanter, KW Sell, F Villinger, CO Siu, A Herskowitz |
Circulation | 1995 |
Systemic release of interleukin-10 during orthotopic liver transplantation
OL Moine, A Marchhant, F Durand, B Ickx, O Pradier, J Belghiti, D Abramowicz, M Gelin, M Goldman, J Devière |
Hepatology | 1994 |
Limiting dilution analysis: quantification of IL-2 producing allospecific lymphocytes after renal and cardiac transplantation
EL Cattell, AC Cunningham, W Bal, RM Taylor, JH Dark, JA Kirby |
Transplant Immunology | 1994 |