Kidney Transplant Patients with Long-Term Graft Survival Have Altered Expression of Molecules Associated with T-Cell Activation

Abstract

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.

Analysis of the peripheral T‐cell repertoire in kidney transplant patients

“…Further studies on sorted Vb families with strong alteration, on reactivity against donor cells and a long-term follow-up of the stable patient cohort are awaited for improving the interpretation of TCR alteration in long-term graft recipient. Combined with other biomarker data [9][10][11] and associated with the expression of inflammation or regulatory-related genes (GZMB, T-bet versus FOXP3) as shown, TCR repertoire categorization might be included in the calculation of a ''composite score'' for the followup of patients to prevent rejection or helping to decide upon immunosuppressant withdrawal.…”

“…Indeed, because T cells have been shown to be involved in both chronic rejection and tolerance [8], we have explored the T-cell repertoire in a cohort of patients with stable kidney graft function. We have previously shown, in a small cohort of patients, that both drug-free operationally tolerant patients (TOL patients) and patients with the ''suspicious'' form of chronic rejection (CHR patients) display a TCR repertoire that differs from healthy, nontransplanted individuals [9][10][11]. In this article, we revisit the relationship between peripheral T-cell repertoire and clinical status, using a new statistical method to analyze the TCR repertoires presented as TcLandscape (TcL) data.…”

Differential monocyte STAT6 activation and CD4+CD25+Foxp3+ T cells in kidney operational tolerance transplanted individuals

“…Total RNA was reversetranscribed using Superscript II reverse-transcriptase, with oligo(dT) [12][13][14][15][16][17][18] primer and random primers (Invitrogen) in a final volume of 20 l. RNA samples were treated with RNase-free DNase I (Invitrogen) before reverse transcription to eliminate contaminating genomic DNA. For detection of IL-4R␣ messenger ribonucleic acid (mRNA), the reaction mixture (10 l) contained 0.3 M of forward and reverse IL-4R␣ primers and the SYBR-Green PCR Master Mix (Applied Biosystems, Foster City, CA), according to the manufacturers' recommendations.…”

“…Although it has been reported that kidney transplanted individuals with long-term graft survival have an altered expression of molecules related with T-cell activation [13], it has not been investigated whether these alterations modulate and activate different signaling pathways. We hypothesize that intracellular signaling pathways activated by cytokines might have an important role in the establishment of tolerance, as cytokines modulate the function and the differentiation of T cells.…”

Lymphocyte surface molecules as immune activation biomarkers

“…On the one hand, increased expression on CD3 cells in peripheral blood was associated with long-term survival of kidney transplants [43] as well as on CD4 cells in patients with stable graft functions compared with those with chronic allograft nephropathy [44]. On the other hand, expression on CD4 cells (together with CD28) was observed to be up-regulated during rejection in liver graft recipients compared with non-rejection patients [24].…”