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1.
J Clin Invest ; 118(8): 2845-57, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18654667

RESUMO

A fraction of liver transplant recipients are able to discontinue all immunosuppressive therapies without rejecting their grafts and are said to be operationally tolerant to the transplant. However, accurate identification of these recipients remains a challenge. To design a clinically applicable molecular test of operational tolerance in liver transplantation, we studied transcriptional patterns in the peripheral blood of 80 liver transplant recipients and 16 nontransplanted healthy individuals by employing oligonucleotide microarrays and quantitative real-time PCR. This resulted in the discovery and validation of several gene signatures comprising a modest number of genes capable of identifying tolerant and nontolerant recipients with high accuracy. Multiple peripheral blood lymphocyte subsets contributed to the tolerance-associated transcriptional patterns, although NK and gammadeltaTCR+ T cells exerted the predominant influence. These data suggest that transcriptional profiling of peripheral blood can be employed to identify liver transplant recipients who can discontinue immunosuppressive therapy and that innate immune cells are likely to play a major role in the maintenance of operational tolerance in liver transplantation.


Assuntos
Perfilação da Expressão Gênica , Tolerância Imunológica , Transplante de Fígado/imunologia , Imunologia de Transplantes/genética , Tolerância ao Transplante/genética , Adulto , Idoso , Antígenos CD4/genética , Estudos de Casos e Controles , Estudos de Coortes , DNA/genética , DNA Viral/genética , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/genética , Rejeição de Enxerto/imunologia , Hepacivirus/genética , Hepacivirus/patogenicidade , Humanos , Imunofenotipagem , Imunossupressores/administração & dosagem , Células Matadoras Naturais/imunologia , Transplante de Fígado/patologia , Pessoa de Meia-Idade , Modelos Genéticos , Modelos Imunológicos , Análise de Sequência com Séries de Oligonucleotídeos , Valor Preditivo dos Testes , Receptores de Antígenos de Linfócitos T gama-delta/genética , Transcrição Gênica
2.
Transpl Int ; 23(10): 1045-55, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20477999

RESUMO

γδ T cells are innate-type lymphocytes that preferentially act as regulators of local effector immune responses. Recent reports found an altered distribution of the two main subpopulations of blood γδ T cells (Vδ1 and Vδ2) in operationally tolerant liver transplant recipients. Based on this, γδ T cells subset quantification was proposed as a biomarker of immunologic risk in liver transplantation. The specific characteristics of γδ T cell subsets in transplantation remain however unknown. We have investigated here the phenotype, repertoire and functional properties of γδ T cell subsets in a large population of allograft recipients. Our results indicate that alterations in the γδ T cell compartment are not restricted to tolerant liver recipients. In fact, most immunosuppressed liver and kidney recipients also display an enlarged peripheral blood γδ T cell pool mainly resulting from an expansion of Vδ1 T cells exhibiting an oligoclonal repertoire and different phenotypic and cytokine production traits than Vδ2 T cells. We propose that persistent viral infections are likely to contribute to these alterations. Our data provide novel insight in the biology of γδ T cells and a rationale for exploring these lymphocytes in more depth into the pathogenesis of viral infections in transplantation.


Assuntos
Transplante de Fígado/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Subpopulações de Linfócitos T/imunologia , Adulto , Idoso , Motivos de Aminoácidos , Quimerismo , Regiões Determinantes de Complementaridade/genética , Citocinas/metabolismo , Feminino , Humanos , Transplante de Rim/imunologia , Masculino , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T gama-delta/genética , Tolerância ao Transplante , Viroses/imunologia
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