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Background: Membrane CD30 is an important costimulatory molecule for activated T lymphocytes, and serum level of soluble CD30 (sCD30) is considered a marker for predicting outcome in kidney transplantation., Methods: We investigated the kinetics of CD30 expression on CD4 and CD8 T-cell populations and the source of sCD30 during alloimmune responses in vitro. The effect of neutralizing antibodies against interferon (IFN)-γ and other cytokines on sCD30 release and the involvement of metalloproteinases ADAM10 and ADAM17/TACE that are responsible for sCD30 shedding were also assessed. Memory phenotypes and CD30 expression on allostimulated CD3 lymphocytes were evaluated in dialysis patients and matched controls., Results: Allogeneic stimulation resulted in conversion of naive responder cells to central memory CD4 cells (P<0.001 at 96 hr) and effector CD8 cells (P<0.01 at 120 hr), which was accompanied by increased CD30 expression. Release of sCD30 was attributed mainly to central memory cells, and neutralization of IFN-γ (P<0.001) and interleukin (IL)-2 (P<0.001) impaired the release of sCD30 during allostimulation but did not alter the levels of ADAM10 and ADAM17/TACE. CD30 expression was modulated in dialysis patients in a similar way as in healthy controls., Conclusions: 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.

Allospecific memory T cells are a barrier against long-term graft survival. Production of multiple cytokines by a single T cell is considered a sign of an active ongoing immune response, the presence of these polyfunctional cells has not been addressed in transplanted patients accordingly to graft outcome. Memory phenotype, based on the expression of CD45RO and CD27, and polyfunctional T cells were evaluated in long-term graft survival patients (LTS), short-term survival patients (STS), chronic rejection patients (ChrRx), dialysis patients (DIAL) and healthy controls (Ctrls). Memory T cells were quantified ex vivo, after allogeneic and anti-CD3 plus anti-CD28 stimulation, in cells proliferating or not to these stimuli. The percentages of cells producing IFNγ, IL-2 and/or TNFα after allogeneic stimulation and the memory phenotype of single cytokine producing cells were evaluated. Ex vivo CD8+CD45RO-CD27- effector cells were decreased in transplanted patients compared to non-transplanted individuals. After allogeneic stimulation, CD4+CD45RO+CD27+, central memory cells in LTS and CD4+CD45RO-CD27- effector cells in Dial were augmented compared to Ctrls and ChrRx, and CD8+CD45RO-CD27- effector cells were increased in ChrRx. There were no differences in the percentage of single cytokine producing cells among the groups. IFNγ+TNFα+CD4 and CD8 cells were detected in Ctrls, STS and ChrRx and no cells positive for the three cytokines were found. The phenotype of cytokine producing cells was mainly effector memory. Interestingly, in LTS there was an increase in effector cells producing IFNγ and IL-2. Changes in subpopulation distribution in patients with different outcomes may be a reflection of the graft acceptance or rejection status., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The mechanisms underlying maintenance of renal allografts in humans under minimal or conventional immunosuppression are poorly understood. There is evidence that CD4(+) CD25(+) regulatory T cells and clonal deletion, among other mechanisms of tolerance, could play a key role in clinical allograft survival. Twenty-four TCR-Vbeta families were assessed in CD4(+) CD25(-), CD4(+) CD25(low) and CD4(+) CD25(high) T cells from patients with long-term renal allograft survival (LTS), patients exhibiting chronic rejection (ChrRx), patients on dialysis (Dial) and healthy controls (HC) by flow cytometry. LTS patients presented a higher variability in their TCR-Vbeta repertoire, such decreased percentage of Vbeta2(+), Vbeta8a(+) and Vbeta13(+) in CD4(+) CD25(low) and (high) compared with CD4(+) CD25(-) subset and increased Vbeta4 and Vbeta7 families in CD4(+) CD25(high) T cells exclusively. Additionally, LTS patients, particularly those that were not receiving calcineurin inhibitors (CNI), had increased percentages of CD4(+) CD25(high) T cells when compared with Dial (P < 0.05) and ChrRx (P < 0.05) patients. Our results suggest that a differential expression of particular TCR-Vbeta families and high levels of circulating CD4(+) CD25(high) T cells in long-term surviving renal transplant patients could contribute to an active and specific state of immunologic suppression. However, the increase in this T cell subset with regulatory phenotype can be affected by CNI.