Tailoring of immunosuppression in renal and liver allograft recipients displaying donor specific T-suppressor cells

Cortesini, Raffaello; Renna-Molajoni, E; Cinti, P; Pretagostini, R.; Ho, Eric K.; Rossi, P; Cortesini, Nicole Suciu-Foca

doi:10.1016/s0198-8859(02)00442-1

Cited by 39 publications

(22 citation statements)

References 43 publications

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“…While most of the recent literature has focused on CD4 + CD25 + T cells with regulatory activity (Field et al, 2001;Piccirillo & Shevach, 2001;Skelsey et al, 2003), there also exist CD8 + T cells that express regulatory functions (Cosmi et al, 2003;Ferguson et al, 2002Ferguson et al, , 2003. These CD8 + T regulatory cells are found in both humans (Cortesini et al, 2002;Filaci & Suciu-Foca, 2002) and mice (Ferguson et al, 2002;Jiang & Chess, 2000;Jiang et al, 2001) and operate in a variety of antigen-specific responses (Ferguson et al, 2002;Nakamura et al, 2003) and diseases (Jiang et al, 2001;Taneja et al, 2002;Zhang et al, 2002). They have also been implicated in viral and parasitic infections (Hafalla et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

CD8+ T cells control corneal disease following ocular infection with herpes simplex virus type 1

Stuart

Summers

Morris

et al. 2004

Journal of General Virology

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The role that T cell subsets play in herpetic stromal keratitis (HSK) has been the subject of intense research efforts. While most studies implicate CD4 + T cells as the principal cell type mediating primary corneal disease, recent reports using knockout mice have suggested that both CD4 + and CD8 + T cell subsets may play integral roles in modulating the disease. Furthermore, recent studies suggest that CD8 + T cells are directly involved in maintaining virus latency in infected trigeminal ganglia. This work has addressed these discrepancies by infecting the corneas of mice lacking CD4 + and CD8 + T cells with herpes simplex virus type 1 (HSV-1) and monitoring both corneal disease and latent infection of trigeminal ganglia. Results indicated that mice lacking CD8 + T cells had more severe corneal disease than either BALB/c or B6 parental strains. In contrast, mice lacking CD4 + T cells had a milder disease than parental strains. When mice were evaluated for persistence of infectious virus, only transient differences were observed in periocular tissue and corneas. No significant differences were found in persistence of virus in trigeminal ganglia or virus reactivation from explanted ganglia. These data support the following conclusions. CD4 + T cells are not required for resistance to infection with HSV-1 and probably mediate HSK. Mice lacking CD8 + T cells do not display differences in viral loads or reactivation and thus CD8 + T cells are not absolutely required to maintain latency. Finally, CD8 + T cells probably play a protective role by regulating the immunopathological response that mediates HSK. INTRODUCTIONHerpetic stromal keratitis (HSK) is a potentially blinding corneal inflammation that accompanies herpes simplex virus (HSV) infection of the eye. The disease course in HSK begins with a primary infection by HSV followed by a period during which the virus enters latency in sensory and autonomic ganglia. Many studies have shown that clinical disease is the result of a cocktail of inflammatory cells consisting of polymorphonuclear leukocytes, macrophages and T cells (both CD4 + and CD8 + ) that are recruited to the corneas of patients with HSK (Maertzdorf et al., 2003;Pepose et al., 1996;Thomas & Rouse, 1997;Youinou et al., 1985Youinou et al., , 1986.Corneas removed from patients requiring corneal transplants due to HSK contain both CD4 + and CD8 + T cells that are specific for HSV-encoded antigens (Koelle et al., 2000). In most models of HSK, T cells are critical to the development of corneal lesions, as athymic nude mice do not display signs of HSK (Metcalf et al., 1979) unless adoptive transfer of T cells is performed (Russell et al., 1984). While most investigators believe that the CD4 + subset of T cells mediates this disease, some reports implicate CD8 + T cells as having a major role in primary HSV keratitis (Akova et al., 1993;Doymaz & Rouse, 1992;Hendricks & Tumpey, 1990;Niemialtowski & Rouse, 1992). Furthermore, when most corneas are immunohistochemically stained for T cell subsets, the predomin...

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Section: Discussionmentioning

confidence: 99%

CD8+ T cells control corneal disease following ocular infection with herpes simplex virus type 1

Stuart

Summers

Morris

et al. 2004

Journal of General Virology

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“…In vivo, la regulación positiva de ILT3 e ILT4 adquiere gran relevancia en el contexto del trasplante de órganos, pues se ha demostrado que células T supresoras CD8+CD28-CD27+ provenientes de pacientes con trasplante de corazón inhiben la regulación positiva de CD80 y CD86 en células presentadoras de antígeno provenientes del donante (89,90) Este efecto inhibidor es restringido por las moléculas CMH de clase I, lo que demuestra la especificidad de antígeno de las células T supresoras. Además, los estudios realizados en células transfectadas con plásmidos que contenían el gen de la luciferasa en el promotor de ILT3 e ILT4, demostraron que las células T supresoras de estos pacientes también inducían la regulación positiva de las moléculas ILT3 e ILT4, en las células presentadoras de antígeno provenientes del donante, donde nuevamente se encontró que la transcripción de estas dos moléculas era restringida por las moléculas CMH de clase I del donante (83).…”

Section: Papel Central De Los Receptores Ilt3 E Ilt4 En La Regulaciónunclassified

“…Además, el aumento de la expresión de ILT4 en los monocitos expuestos a suero de pacientes infectados con VIH, resulta en la inhibición de la activación y la proliferación de células T CD4+ (90). Este hallazgo sugiere que algunos medicamentos podrían bloquear esas moléculas, pudiendo tener un valor terapéutico significativo para el tratamiento de estos pacientes.…”

Section: Proteasomaunclassified

Papel de las células dendríticas tolerogénicas ILT3+/ILT4+ en la respuesta inmunitaria a trasplante de órganos y tejidos

Arboleda¹,

García²,

Álvarez³

2011

biomedica

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Las células dendríticas son las células presentadores de antígeno más potentes y, por lo tanto, son importantes en el desencadenamiento de la respuesta inmunitaria frente a aloantígenos; sin embargo, también juegan un papel fundamental en el mantenimiento de la tolerancia periférica. La tolerancia es potenciada por la expresión en estas células de los receptores inhibidores ILT3 e ILT4, los cuales, mediante el reclutamiento de fosfatasas de tirosinas a sus dominios ITIM, inhiben la activación de la célula presentadora de antígeno y conducen a una débil respuesta de la célula T. Estos receptores propician, además, una interacción bidireccional con células T supresoras, T reguladoras o ambas, generando una cascada inmunorreguladora específica de antígeno, en la cual la célula dendrítica se comporta como una célula "tolerogénica". En esta revisión analizamos la biología y el comportamiento de las células dendríticas tolerogénicas que expresan altos niveles de ILT3 e ILT4, así como algunos aspectos moleculares y genéticos de estos receptores y su importancia en la modulación de las respuestas inmunitarias específicas de aloantígeno frente a un trasplante.Palabras clave: trasplante, células dendríticas, tolerancia inmunológica, inmunomodulación, supervivencia. ILT3 + /ILT4 + tolerogenic dendritic cells and their influence on allograft survivalDendritic cells, the most powerful antigen-presenting cells, are important for triggering of the immune responses to allo-antigens. However, they also play a fundamental role in the peripheral tolerance maintenance. Tolerance is enhanced by the presence on the dendritic cell surface of the inhibitor receptors ILT3 and ILT4. They recruit protein tyrosine-phosphatases to their ITIM domains and inhibit antigen-presenting cell activation, leading T cell hypo-responsivensess. Moreover, these receptors favor a bidirectional interaction with T-suppressor and T-regulator cells, generating an antigen-specific immunoregulator cascade, in which the dendritic cell behaves as a tolerogenic cell. In the current review, analysis is centered on the biology and behavior of the tolerogenic dendritic cells that express high levels of ILT3 and ILT4. Some molecular and genetics aspects of these receptors are discussed as well as their importance in the modulation of the allo-specific antigen immune response to transplants.

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“…Ϫ phenotype also has been reported to be associated with lower rates of rejection and an increased likelihood of being weaned effectively from immunosuppression in kidney and liver transplant recipients (60). Although quantification and characterization of regulatory T cells has the potential to identify patients with predilection toward "tolerance," no systematic studies have been performed to date.…”

Section: Cd28mentioning

confidence: 99%

How Can We Measure Immunologic Tolerance in Humans?

Najafian

Albin²,

Newell³

2006

Journal of the American Society of Nephrology

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Prevention and treatment of allograft rejection in organ transplant recipients relies primarily on non-antigen-specific immunosuppression, with all its associated potential hazards and costs. Currently, the status of the recipient immune response is measured by monitoring pharmacologic drug levels and clinical/pathologic evaluation of graft function. Development of reliable assays that can measure accurately the status of the immune response not only would help clinicians customize the prescription of immunosuppressive drugs in individual patients but also may allow their complete withdrawal in some patients with immunologic tolerance. Furthermore, these assays would facilitate the safe evaluation of novel tolerogenic regimens. Achieving this goal has proved to be very difficult because it requires both a more in-depth understanding of complex mechanisms of tolerance and also identification of transplant patients with acquired tolerance to an allograft that can be studied. This review discusses the current understanding of tolerance mechanisms and outlines the unique and specific challenges in development of tolerance/monitoring assays in the field of transplantation. In addition, several of the most promising candidate assays are discussed in detail.

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Tailoring of immunosuppression in renal and liver allograft recipients displaying donor specific T-suppressor cells

Cited by 39 publications

References 43 publications

CD8+ T cells control corneal disease following ocular infection with herpes simplex virus type 1

CD8+ T cells control corneal disease following ocular infection with herpes simplex virus type 1

Papel de las células dendríticas tolerogénicas ILT3+/ILT4+ en la respuesta inmunitaria a trasplante de órganos y tejidos

How Can We Measure Immunologic Tolerance in Humans?

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