Immunological tolerance and liver transplantation

Sánchez‐Fueyo, Alberto; Strom, Terry B.

doi:10.1016/j.jhep.2004.09.013

Cited by 32 publications

(24 citation statements)

References 58 publications

(70 reference statements)

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“…Indeed, accumulated experiences indicate that IS can be completely withdrawn in 20% of selected liver recipients (12), and these patients are considered as 'operationally' tolerant. A variety of different immunological mechanisms appear to contribute to the spontaneous acceptance of liver grafts (13). However, none of these mechanisms has been convincingly validated in humans yet.…”

Section: Introductionmentioning

confidence: 99%

Multiparameter Immune Profiling of Operational Tolerance in Liver Transplantation

Martínez‐Llordella

Puig-Pey

Orlando

et al. 2007

American Journal of Transplantation

336

288

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Immunosuppressive drugs can be completely withdrawn in up to 20% of liver transplant recipients, commonly referred to as 'operationally' tolerant. Immune characterization of these patients, however, has not been performed in detail, and we lack tests capable of identifying tolerant patients among recipients receiving maintenance immunosuppression. In the current study we have analyzed a variety of biological traits in peripheral blood of operationally tolerant liver recipients in an attempt to define a multiparameter 'fingerprint' of tolerance. Thus, we have performed peripheral blood gene expression profiling and extensive blood cell immunophenotyping on 16 operationally tolerant liver recipients, 16 recipients requiring on-going immunosuppressive therapy, and 10 healthy individuals. Microarray profiling identified a gene expression signature that could discriminate tolerant recipients from immunosuppression-dependent patients with high accuracy. This signature included genes encoding for c d T-cell and NK receptors, and for proteins involved in cell proliferation arrest. In addition, tolerant recipients exhibited significantly greater numbers of circulating potentially regulatory T-cell subsets (CD4 + CD25 + T-cells and Vd1 + T cells) than either non-tolerant patients or healthy individuals. Our data provide novel mechanistic insight on liver allograft operational tolerance, and † Deceased 12/9/2005 constitute a first step in the search for a non-invasive diagnostic signature capable of predicting tolerance before undergoing drug weaning.

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Section: Introductionmentioning

confidence: 99%

Multiparameter Immune Profiling of Operational Tolerance in Liver Transplantation

Martínez‐Llordella

Puig-Pey

Orlando

et al. 2007

American Journal of Transplantation

336

288

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“…It is well known that the difficulty of tolerance induction depends on different organs transplantation. Because the liver has proved to be an immunologically privileged organ, capable in several animal models to be accepted as an allograft without any intervention by the immune system of the recipient, grafted liver survived longer than other grafted organs (Raimondo and Burroughs, 2002;Alberto and Terry, 2004). Bone marrow combined with solid organ transplantation was often used in research on induction of chimerism and immunotolerance, based on cardiac, skin and kidney transplantations.…”

Section: Discussionmentioning

confidence: 99%

“…2003CB515501) supported by the National Basic Research Program (973) of China result, the donor liver avoids attack by the recipient immunity system and prevents rejection after transplantation. Clinical investigations have shown that some transplantation recipients would survive with normal liver function after withdrawal of immunosuppressants (Raimondo and Burroughs, 2002;Alberto and Terry, 2004). Therefore, it is acknowledged that the liver is prone to tolerate allografts.…”

Section: Introductionmentioning

confidence: 99%

Infusion of nonmyeloablative bone marrow alleviates acute rejection reaction in liver allotransplantation

Xie

Huang

Chen

et al. 2005

J. Zhejiang Univ. - Sci. B

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Abstract:Objective: To study the effect and implication of nonmyeloablative donor specific bone marrow (DSBM) infusion on the immunoreaction of liver allotransplantation. Methods: Orthotopic liver transplantation model was used in this study. Groups were set as follows: Group I, syngeneic control (Wistar-to-Wistar); Group II, acute rejection (SD-to-Wistar); Group III, acute rejection treated with cyclosporine A (CsA) by intramuscular injection (SD-to-Wistar+CsA); Group IV, bone marrow infusion at 7 d pretransplantation followed by short-term CsA treatment (SD-to-Wistar+DSBM); Another group of short-term CsA treatment preoperatively without bone marrow infusion was also set as control. General characteristics and survival time were observed. Histological grades of rejection were determined by pathological examination. IL-2 and IFN-γ level in peripheral blood and donor liver were detected respectively by Enzyme-Linked Immuno-Sorbent Assay (ELISA) and Western blot. Chimerism of donor cells was measured by PCR for a male-specific marker (Y-chromosome-specific sequence, Sry). Results: No signs of rejection were found in Group I. Acute rejection occurred in both Group II and the short-term CsA treated group. All the recipients died at (9~15) d posttransplantation with a median survival time of (10.7±0.5) d and (11.2±2.4) d, respectively. Only mild rejection could be seen in Group III. In Group IV, 4 out of 6 recipients had long-term survival (>100 d), the histological grade of rejection was significantly lower than that of Group II, so did the expression level of IL-2 and IFN-γ in both peripheral blood and grafted liver. Y-chromosome-specific sequence (Sry) of male SD rats could be detected in the bone marrow, spleen and thymus of female recipients at 15 d after bone marrow infusion. Conclusion: Mild preconditioning nonmyeloablative donor specific bone marrow infusion can enhance chimerism formation in recipients, alleviate the rejection of liver allotransplantation and prolong survival of liver allotransplantation.

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“…El trasplante hepáti-co protege habitualmente al riñon trasplantado del mismo donante, del rechazo agudo humoral y celular (47). En pacientes trasplantados hepáticos seleccionados es posible retirar definitivamente toda la inmunosupresión hasta en un 25-30% de casos (7-10), permaneciendo sanos en algunos casos hasta 30 años después de la retirada, lo que viene considerándose una tolerancia "operacional" (12).…”

Section: El Fenómeno De La Tolerancia Del Injerto Hepáticounclassified

“…Esta observación en animales y la posibilidad de retirar completamente los fármacos inmunosupresores en pacientes seleccionados con trasplante hepático (7)(8)(9)(10), nos permite afirmar que el híga-do es un órgano inmunológicamente privilegiado (11), que puede tolerarse tras el trasplante con menor inmunosupresión y en ocasiones es posible retirar completamente los fármacos inmunosupresores (tolerancia operacional) (12). Datos experimentales apoyarían la idea de poder inducir tolerancia en humanos sometidos a trasplante de órganos.…”

Section: Introductionunclassified

Tolerancia y quimerismo en el trasplante hepático

Miñano

Romero

Campos

et al. 2007

Rev. esp. enferm. dig.

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INTRODUCCIÓNLos avances en el tratamiento inmunosupresor han tenido un gran impacto en la evolución y en el éxito de los trasplantes de órganos y en particular del trasplante hepá-tico. Con la introducción de los nuevos fármacos inmunosupresores, la incidencia de rechazo agudo ha disminuido de forma considerable, y la supervivencia de los pacientes trasplantados hepáticos es del 83 y del 70% al año y 5 años respectivamente (1). Sin embargo, la toxicidad asociada con el uso de estos fármacos es importante, condicionando la aparición de hipertensión arterial, hiperlipemia, diabetes, insuficiencia renal y tumores de novo en los pacientes trasplantados (2,3). Por todo ello, y para mejorar la eficacia y la especificidad de los tratamientos inmunosupresores, es imprescindible profundizar en el conocimiento de los mecanismos de la respuesta alogénica primaria contra antígenos extraños y en los mecanismos de tolerancia específica de antígeno, para que nos pueda ayudar a evitar o disminuir al máximo posible el uso de fármacos inmunosupresores.Es un hecho conocido que el trasplante hepático entre especies animales como el cerdo y entre ciertas combinaciones de ratas y ratones, puede realizarse sin inmunosupresión (4-6). Esta observación en animales y la posibilidad de retirar completamente los fármacos inmunosupresores en pacientes seleccionados con trasplante hepático (7-10), nos permite afirmar que el híga-do es un órgano inmunológicamente privilegiado (11), que puede tolerarse tras el trasplante con menor inmunosupresión y en ocasiones es posible retirar completamente los fármacos inmunosupresores (tolerancia operacional) (12). Datos experimentales apoyarían la idea de poder inducir tolerancia en humanos sometidos a trasplante de órganos. Aunque la tolerancia sería el objetivo ideal, la heterogeneidad de combinaciones posibles entre donante y receptor, el estado inmune del receptor, la enfermedad de base del paciente trasplantado, y las consecuencias imprevisibles de las infecciones hacen que una tolerancia estable sea extremadamente difí-cil en todos los pacientes (13).La tolerancia en el ámbito del trasplante sería la falta de respuesta inmune a los aloantígenos (antígenos extraños) del órgano trasplantado, en ausencia de inmunosupresión (14). El fenómeno de tolerancia inmunológica es la ausencia de respuesta a un antígeno con el que ha habido un encuentro propio, y es por tanto, un fenómeno activo (15). La tolerancia a antígenos propios, al igual que la tolerancia a los aloantígenos es una función del sistema inmune. Los mecanismos implicados en la tolerancia a los órganos trasplantados son complejos y no totalmente conocidos. El objetivo de esta revisión es describir los mecanismos implicados en la tolerancia, en especial en el ámbito del trasplante hepático, destacando el papel del quimerismo celular y los fenómenos de inmunorregulación en el desarrollo de tolerancia. ALORRECONOCIMIENTO Y RECHAZOEl sistema inmune funciona diferenciando lo propio de lo extraño. Concretamente, el término alorreconoci- 343-350.

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Immunological tolerance and liver transplantation

Cited by 32 publications

References 58 publications

Multiparameter Immune Profiling of Operational Tolerance in Liver Transplantation

Multiparameter Immune Profiling of Operational Tolerance in Liver Transplantation

Infusion of nonmyeloablative bone marrow alleviates acute rejection reaction in liver allotransplantation

Tolerancia y quimerismo en el trasplante hepático

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