Identification of a peripheral blood transcriptional biomarker panel associated with operational renal allograft tolerance.

Long-term allograft survival generally requires lifelong immunosuppression (IS). Rarely, recipients display spontaneous "operational tolerance" with stable graft function in the absence of IS. The lack of biological markers of this phenomenon precludes identification of potentially tolerant patients in which IS could be tapered and hinders the development of new tolerance-inducing strategies.

Development of CD25- regulatory T cells following heart transplantation: evidence for transfer of long-term survival.

Donor-specific heart allograft acceptance can be induced in the MHC-mismatched LEW.1 W to LEW.1A rat by donor-specific transfusions.

Dominant tolerance to kidney allografts induced by anti-donor MHC class II antibodies: cooperation between T and non-T CD103+ cells.

Allograft acceptance can be induced in the rat by pretransplant infusion of donor blood or spleen cells. Although promoting long-term acceptance, this treatment is also associated with chronic rejection. In this study, we show that a single administration of anti-donor MHC class II alloimmune serum on the day of transplantation results in indefinite survival of a MHC-mismatched kidney graft.

Contrasting CD25hiCD4+T cells/FOXP3 patterns in chronic rejection and operational drug-free tolerance.

Background: Although immunosuppression withdrawal in kidney recipients usually leads to rejection, in some patients it does not, leading to a state of clinical operational tolerance.

Methods: We compared these highly contrasted situations by analyzing blood cell phenotype and transcriptional patterns in drug-free spontaneously tolerant kidney recipients, recipients with chronic rejection, recipients with stable graft function under standard or minimal immunosuppression and healthy individuals

Results: The blood cell phenotype of clinically tolerant patients did not differ from that of healthy individuals. In contrast, recipients with chronic rejection had significantly less CD25hiCD4+T cells and lower levels of FOXP3 transcripts compared with clinically tolerant recipients.

Operationally tolerant and minimally immunosuppressed kidney recipients display strongly altered blood T-cell clonal regulation.

Most kidney transplant recipients who discontinue immunosuppression reject their graft. Nevertheless, a small number do not, suggesting that allogeneic tolerance state (referred to operational tolerance) is achievable in humans. So far, however, the rarity of such patients has limited their study.

Blood T-cell Vbeta transcriptome in melanoma patients.

Tumor-cells have been shown to elicit MHC-restricted and antigen-specific T-cell responses. In this article, we used a new approach to study T-cell responses in tumor-bearing patients based on a global representation of the Vbeta-transcriptome, making it possible to grade CDR3-length distribution (CDR3-LD) alterations. Six patients with advanced melanoma disease, from whom blood samples were taken before and serially after tyrosinase-A peptide vaccination, were studied.