Approaches to transplantation tolerance in humans

Strober, Samuel; Lowsky, Robert; Shizuru, Judith A.; Scandling, John D.; Millan, Maria T.

doi:10.1097/01.tp.0000117782.93598.6e

Cited by 42 publications

(24 citation statements)

References 31 publications

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“…79 As a pretransplantation conditioning regimen, TLI has induced tolerance in chimeric and nonchimeric humans, whereas posttransplantation irradiation has failed to produce stable chimeras or tolerance. 80 …”

Section: Tlimentioning

confidence: 99%

Frontiers in Nephrology

Girlanda

Kirk

2007

Journal of the American Society of Nephrology

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Section: Tlimentioning

confidence: 99%

Frontiers in Nephrology

Girlanda

Kirk

2007

Journal of the American Society of Nephrology

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“…Briefly, three out of four such patients developed transient microchimerism, lasting less than three months, and two were withdrawn from immunosuppression at 1 year based on donor-specific unresponsiveness by mixed lymphocyte reaction (MLR). Both experienced acute rejection five months later that was reversed with steroids and both had reinstitution of immunosuppression (Strober et al 2004). A related mechanistic explanation of tolerance has been developed by Thompson et al who propose that an important cell regulating tolerance is the dendritic cell.…”

Section: Chimerism and Tolerancementioning

confidence: 98%

Development of tolerogenic strategies in the clinic

Knechtle

2005

Phil. Trans. R. Soc. B

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The study of tolerance in the clinic can be divided into three areas: (i) focused evaluation of existing tolerant transplant recipients as to their mechanism of tolerance; (ii) prospective tolerance trials, such as combined bone marrow and kidney transplantation as well as T cell depletion followed by subsequent weaning of immunosuppression; and (iii) immunologic assays to assess the likelihood of rejection or tolerance. Frankly, a very small number of patients have been transplanted with the intention of removing all immunosuppressive therapy, but several clinical trials with this aim are currently in progress, largely sponsored by the Immune Tolerance Network, a joint venture between the National Institutes of Health and the Juvenile Diabetes Research Foundation. Similarly, a reliable assay to assess tolerance has not yet been developed but a variety of approaches towards assessing rejection, and in some cases tolerance, are being developed. It would be accurate to state that many of the experimental and preclinical approaches to the induction of tolerance have resulted in better immunosuppression for human transplantation, but reliable tolerance strategies in humans have not yet been achieved. Combined bone marrow and kidney transplantation may be considered as one exception to this, but such a strategy is not generally applicable to the vast majority of solid organ transplant recipients. This review will summarize efforts to date, particularly focusing on kidney transplantation.

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“…One of these reports discusses three patients that have become tolerant with this preconditioning regimen (54,71). Another report describes four patients, two of which were withdrawn from immunosuppression but experienced treatable rejection episodes (72). A third describes a patient who has been off immunosuppression for more than 28 mo (73).…”

Section: Tolerance Inductionmentioning

confidence: 99%