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Allostimulation results in the up-regulation of the T-cell activation marker CD30 on CD4 as well as CD8 memory T cells and increased release of sCD30 from these cells in an IFN-γ- and IL-2-dependent manner. These results may explain clinical findings on the suitability of sCD30 and IFN-γ- and IL-2-producing T cells for immune monitoring of kidney transplant recipients before and after transplantation.

Our results suggest that high expression of FOXP3 and chemokine receptor genes in LTS patients are possible indicators of a regulatory process that contributes to long-term allograft acceptance. Markers that were increased in LTS patients were found to be decreased in ChrRx patients, suggesting that rejection may partly be the result of a lack of this regulatory process. FOXP3 and CCR7 and CXCR4 transcripts might be used as markers to distinguish patients who developed long-term allograft acceptance from patients who are prone to ChrRx.

The mechanisms underlying long-term acceptance of kidney allografts in humans under minimal or no maintenance immunosuppression are poorly understood. We analyzed the T-cell receptor (TCR) repertoires in circulating T cells of patients with long-term (≥9 years) renal allograft survival with (LTS-IS) and without immunosuppression (LTS-NoIS). T cells of LTS patients exhibited strongly altered TCR Vß usage, including an increased frequency of oligoclonality and a decreased frequency of polyclonality. All 3 LTS-NoIS and 12 of 16 LTS-IS patients demonstrated oligoclonality in at least three or more TCR Vß families, and the frequency of oligoclonality in these patients was significantly higher as compared to patients with well-functioning grafts at 3 years (p < 0.005 both), an uncomplicated course during the first year (p < 0.0001, both), acute rejection (p < 0.0001, both), chronic allograft nephropathy at 7 (p < 0.0001, both) or 13 years (p < 0.0001, both), dialysis patients (p < 0.0001, both) or healthy controls (p < 0.0001, both). In contrast to LTS patients, all other studied patient groups exhibited a polyclonal TCR repertoire. Our data indicate that TCR alteration is a common feature of long-term allograft outcome, which might be explained by clonal deletion, exhaustion of alloreactive T cells or predominant expression of particular T-cell subpopulations, such as regulatory T cells.

The decreased expression of TCR-alphabeta and epsilon- and zeta-chains on circulating T cells of long-term surviving patients suggests that these cells may have defects in alloantigen recognition or signal transduction that may result in decreased numbers of T cells expressing co-stimulatory molecules and activation markers as well as a decreased specific proliferative response. The decrease in the percentage of CD28(+) cells and the increase in CD4(+)CD25(+)CD69(+) cells suggest that regulatory mechanisms of the immune response are still active in such patients.

HIV infection induces immune alterations, mainly in gut mucosa, where the main target cells reside. However, the evolution of the infection is variable among infected individuals, as evidenced by HIV controllers who exhibit low or undetectable viral load in the absence of treatment. The aim of this study was to evaluate the frequency, phenotype and activity of T and NK cells in peripheral blood and gut mucosa in a cohort of Colombian HIV controllers. Blood and gut biopsies were included. The frequency and the activation status of T and NK cells were performed by flow cytometry. In addition, Gag-stimulated CD8+ T-cells and cytokine-stimulated NK cells were tested for cytotoxic activity. Finally, microbial translocation was measured by plasma lipopolysaccharide quantification. Compared with HIV-progressors, HIV controllers exhibited higher frequency of CD4+ T and NK cells, and lower expression of activation molecules in blood and mucosal immune cells, as well as lower microbial translocation. An increased production of molecules associated with cytotoxic activity of CD8+ T-cells in blood and mucosa and a higher percentage of polyfunctional CD8+ T cells in blood were also observed in HIV controllers. In addition, an increased activity of NK cells was observed in blood. These findings suggest that HIV controllers have a potent immune response, mainly mediated by cytotoxic cells that control HIV replication, which contribute to reducing alterations at the gut mucosa.

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Background We recently demonstrated that donor-derived modified immune cells (MICs)—PBMCs that acquire immunosuppressive properties after a brief treatment— induced specific immunosuppression against the allogeneic donor when administered prior to kidney transplantation. We found an up to 68-fold increase in CD19+CD24hiCD38hi transitional B lymphocytes compared with transplanted controls. Methods Ten patients from a phase I clinical trial who had received MIC infusions before kidney transplantation were followed to posttransplant day 1080. Results Patients treated with MICs had a favorable clinical course, showing no donor-specific HLA antibodies or acute rejections. The four patients who had received the highest dose of MICs 7 days before surgery and were on reduced immunosuppressive therapy showed an absence of in vitro lymphocyte reactivity against stimulatory donor blood cells, whereas reactivity against third-party cells was preserved. In these patients, numbers of transitional B lymphocytes were 75-fold and 7-fold higher than in 12 long-term survivors on minimal immunosuppression and four operationally tolerant patients, respectively (P<0.001 for both). In addition, we found significantly higher numbers of other regulatory B lymphocyte subsets, and a gene expression signature suggestive of operational tolerance in three of four patients. In MIC-treated patients, in vitro lymphocyte reactivity against donor blood cells was restored after B lymphocyte depletion, suggesting a direct pathophysiological role of regulatory B lymphocytes in donor-specific unresponsiveness. Conclusions These results indicate that donor-specific immunosuppression after MIC infusion is long-lasting and associated with a striking increase in regulatory B lymphocytes. Donor-derived MICs appear to be an immunoregulatory cell population which, when administered to recipients prior to transplantation, may exert a beneficial effect on kidney transplants.