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Background and objectives The objective of this study was to characterize CD4+ and CD8+ T-cell populations in blood and urine of renal transplant patients with BK virus ( BKV) infection or allograft rejection. Materials and methods Percentages and absolute numbers of CD4+ and CD8+ effector memory T-cell subtype (TEM) and terminal differentiated T cells (TTD) in renal transplant patients with BKV infection ( n = 14), with an episode of allograft rejection ( n = 9), and in uncomplicated renal transplant patients with a stable kidney function ( n = 12) were measured and compared using 4-color fluorescence-activated cell sorting. Results were correlated with the number of CD4+ and CD8+ T cells in renal biopsies. Results In patients with allograft rejection, the number of urinary CD4+ TEM and CD8+ TEM cells was significantly increased compared to patients with BKV infection or patients without complications. Positive correlation was found between the number of CD4+ and CD8+ cells in the renal biopsies and the number of CD4+ and CD8+ cells in urine. In patients with rejection, after 2 months of immunosuppressive therapy, a reduction in urinary CD8+ TEM cells was found. Conclusions CD4+ TEM and CD8+ TEM cells in urine could be a marker to distinguish allograft rejection from BKV-associated nephropathy and to monitor therapy effectiveness in renal transplant patients with allograft rejection. [ABSTRACT FROM AUTHOR]

Objectives: Programmed death (PD)-1 is a cell death receptor that, upon stimulation, leads to apoptosis. Previous studies have shown alteration of PD-1 expression on T cells and PD-1 genes in patients with systemic lupus erythematosus (SLE). The aim of this study was to assess the expression of this receptor on effector T cells in patients with SLE. Method: In this study we enrolled 32 SLE patients and 31 healthy controls. T cells from peripheral blood were analysed by flow cytometry for the expression of PD-1. Interferon (IFN)-γ and interleukin (IL)-17-producing cells were investigated for the expression of this co-stimulatory marker. Results: Percentages of CD4+ T cells expressing PD-1 were significantly increased in patients with SLE compared to healthy controls. The percentage of PD-1 expression was correlated with the production of INF-γ (r = 0.83, p < 0.0001). We also investigated the production of IL-17 by PD-1+ CD3+ T cells. Inactive patients (3.2 ± 1.2% vs. 5.9 ± 3.5%, p = 0.002) and patients without lupus nephritis (LN) (3.2 ± 1.5% vs. 5.9 ± 3.5%, p = 0.005) showed lower levels of IL-17 compared to healthy controls. Conclusion: We have demonstrated increased expression of PD-1 on CD4+ T cells in SLE patients and an association between PD-1 expression on CD4+ T cells and IFN-γ expression on CD3+ T cells. We have also shown that there is an altered subset of PD-1+ T cells in inactive patients and patients without LN producing lower amounts of IL-17. [ABSTRACT FROM AUTHOR]

Peripheral immunoregulation depends on T regulatory cell trafficking into the allograft to modulate the local alloresponse. Little is known about the relevance of trafficking receptors for Tregs after solid organ transplantation in humans. In this study, expression of the peripheral chemokine receptors CXCR3 and CCR5 on CD4+ FOXP3+ Treg cells was analysed and correlated with allograft function in renal transplant recipients. Flow cytometry analysis of peripheral blood mononuclear cells of 54 renal transplant recipients receiving a calcineurin inhibitor-based immunosuppression was performed for CD4, CD25, FOXP3, CXCR3 and CCR5 within the first 18 months post-transplantation. Correlation analysis of chemokine receptor expression and glomerular filtration rate as calculated by MDRD (eGFR) was performed. Expression of the peripheral homing receptors CXCR3 ( r = 0.44, P < 0.05) and CCR5 ( r = 0.45, P < 0.05) on FOXP3+ Tregs correlated with renal allograft function (eGFR) in patients receiving tacrolimus ( n = 28), but not cyclosporine A (CsA) ( n = 26). CsA but not tacrolimus reduced surface expression of CXCR3 on FOXP3+ Tregs in renal transplant recipients as correlated to trough levels ( r = −0.42, P < 0.05). In contrast to CD4+ CXCR3+ CD25lo T cells, flow-sorted CD4+ CXCR3+ CD25hi Tregs isolated from healthy individuals did not produce IFNγ or IL-17 ex vivo and expressed high levels of GARP mRNA both at baseline as well as after TCR activation indicating functional regulatory activity. Expression of the peripheral trafficking receptors CXCR3 and CCR5 on FOXP3+ Tregs is associated with renal allograft function. These results suggest that Treg trafficking may also depend on the interaction of CXCR3 or CCR5 and their respective ligands. [ABSTRACT FROM AUTHOR]

Summary The peripheral chemokine receptors chemokine receptor 3 (CXCR3) and CC chemokine receptor 5 (CCR5) have been reported to be associated with allograft rejection. The impact of the expression of immunosuppressive drugs on peripherally circulating CD4+ T cell subsets after renal transplantion is unknown. Expression of CXCR3 and CCR5 was investigated by flow cytometry in 20 renal allograft recipients participating in a prospective, randomized trial (NCT00514514). Initial immunosuppression consisted of basiliximab, cyclosporin A (CsA), mycophenolate sodium and corticosteroids. After 3 months, patients were treated either with CsA, mycophenolate sodium (MPA) plus corticosteroids ( n = 6), CsA and everolimus plus corticosteroids ( n = 8) or CsA-free (CsAfree) receiving everolimus, MPA and corticosteroids ( n = 6). After initial reduction of CD4+forkhead box protein 3 (FoxP3)+ and CD4+CD25hiFoxP3+ regulatory T cells (Tregs) ( P < 0·05; P < 0·01), 3-month post-transplant percentages of Tregs were reconstituted in CsAfree and CsAlo arms compared to CsAreg 12 months post transplant. Expression of CCR5 and CXCR3 on CD4+FoxP3+ and CD4+FoxP3- T cells 12 months post transplant was increased in CsAfree versus CsAreg. Increase in CCR5+CXCR3+ co-expressing CD4+FoxP3- cells between 3 and 12 months correlated negatively with the glomerular filtration rate (GFR) slope/year [modification of diet in renal disease (MDRD); r = −0·59, P < 0·01]. CsA, but not everolimus, inhibits both Treg development and expression of CXCR3 and CCR5 on CD4+ T cell subsets. Increase in CCR5+CXCR3+ co-expressing CD4+FoxP3- T cells is associated with early loss in allograft function. [ABSTRACT FROM AUTHOR]

B cells, being a source of characteristic antinuclear autoantibodies, play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE). Evidences indicate that alterations in B-cell regulation are responsible for B-cell hyperactivity as seen in SLE. T cells, soluble factors, and even B cells themselves regulate effector B-cell functions. The latter, so-called regulatory B cells possess regulatory function through production of the cytokine interleukin-10 (IL-10) that can damp down the humoral immune responses. This review will focus on B-cell regulation in the pathogenesis of SLE as a target for intervention. In particular, the regulatory impact of T cells through costimulation, soluble factors such as B lymphocyte stimulator, and the characteristics of IL 10-producing regulatory B cells will be discussed. Therapies targeting B cells as well as B-cell regulation seem promising, but the precise mechanisms involved in these interventions are not completely understood. More insight into B-cell regulation in SLE, and particularly in regulatory B cells, could lead to novel therapeutic strategies. [ABSTRACT FROM AUTHOR]