Immune Deficiency in Uremia: Interleukin-2 Production and Responsiveness and Interleukin-2 Receptor Expression and Release

Donati, D; Degiannis, Dimitrios; Homer, Leroy; Gastaldi, L; Rašková, Jana; Raska, K

doi:10.1159/000186435

Cited by 36 publications

(17 citation statements)

References 26 publications

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“…In vitro soluble IL-2R released from mitogen-stimulated human peripheral blood lymphocytes can bind IL-2 and inhibit IL-2-dependent cell proliferation [35]. Our findings of increased sIL-2R levels in plasma are consistent with those of others [34, 36, 37]. IL-2Rα seems to undergo substantial renal clearance [34].…”

Section: Discussionsupporting

confidence: 88%

“…As T cells produce IL-2, the decreased number of CD4+ cells partly explains the suppressed IL-2 production [33]. However, another report [34]showed that the in vitro production of IL-2 is similar in T cells from patients and controls. In vitro soluble IL-2R released from mitogen-stimulated human peripheral blood lymphocytes can bind IL-2 and inhibit IL-2-dependent cell proliferation [35].…”

Section: Discussionmentioning

confidence: 99%

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Characteristic Cytokine Products of Th1 and Th2 Cells in Hemodialysis Patients

Daichou

Kurashige

Hashimoto

et al. 1999

Nephron

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Dysfunction of the host defense against infection in hemodialysis (HD) patients has major clinical and socioeconomic implications. T helper type 1 (Th1) and type 2 (Th2) cytokines are implicated in regulating the immune responses and, therefore, may be involved in impaired status. The present study was designed to examine Th1 and Th2 cytokine profiles in 22 stable HD patients (aged 63 ± 11 years) and 22 healthy controls (aged 60 ± 6 years). The T cell activity was significantly retarded in HD patients as compared with normal persons. The proportions of T cytotoxic/suppressor cells and natural killer cells were significantly higher in HD patients than in controls. In contrast, the proportions of T helper/inducer and B cells were significantly lower in HD patients than in controls. The production of interleukin (IL) 2, which is involved in cell-mediated immune responses, and the production of IL-4 and IL-10, which affect humoral immunity, were significantly lower in patients than in controls. The production of IL-12 by macrophages and of interferon gamma by Th1 cells was significantly higher in HD patients than in controls. The concentration of plasma sIL-2R was significantly higher in patients than in controls. These results suggest that both cellular immunity induced by Th1 and humoral immunity induced by Th2 decrease in HD patients, but that improved IL-12 secretion by macrophages activated natural killer cells to produce interferon gamma, which in turn induced macrophage activity.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Characteristic Cytokine Products of Th1 and Th2 Cells in Hemodialysis Patients

Daichou

Kurashige

Hashimoto

et al. 1999

Nephron

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“…In particular polymorphonuclear granulocytes and/or monocytes, are probably more prominent in the effector phase of active WG. Although retention of slL-2R with impaired renal function has been suggested [38], our findings can not be explained as a result of progressive renal failure during major disease activity, since there was no correlation between sIL-2R levels in those patients and creatinine clearance (data not shown). Others also have suggested overproduction of sIL-2R as a more important factor than metabolic retention to explain the observed high levels of sIL-2R in patients with renal vasculitis [37].…”

Section: Discussioncontrasting

confidence: 53%

Serum markers of T cell activation in relapses of Wegener's granulomatosis

Stegeman¹,

Tervaert²,

Huitema³

et al. 1993

Clinical and Experimental Immunology

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SUMMARYLevels of soluble IL-2 receptor (sIL-2R). soluble CD4 {sCD4) and CD8 (sCD8) were measured by sandwich ELISA as markers for T cell activation in serial serum samples from 16 patients showing 18 histologicaliy proven relapses of Wegener's granulomatosis (WG). Levels of sIL-2R increased from 1065 U/ml (median, range 373-2345 U/ml)6monthsbefore the relapse to 1684 U/ml (median, range 486-3404 U/ml) at the moment of relapse for the whole group (P^OIO). The eight major relapses showed a profound rise in s!L-2R levels, from 1008 U/ml (median, range 686-1553 U/ml) 6 months before the relapse, to 1994 U/ml (median, range 1469-3404 U/ml) at the moment of relapse (/»< 0 01), The levels of sIL-2R at the moment of relapse were significantly higher at the eight major relapses than at the time of the 10 minor relapses (/'<0 05). Minor relapses were not accompanied by a significant rise in slL-2R levels. Titresofantineutrophilcytoplasmic antibodies (ANCA) rose by two or more titresteps or from negative to positive in 15/18 patients during the 6 months period before the relapse. In all seven cases with both a rise of the ANCA titreand an at least 15"At Increase in sIL-2R levels, the rise in ANCA preceded the rise in sIL-2R by at least 1 month, The level of slL-2R at the moment of relapse correlated with the level of C-reactive protein (r = 0 488. /'<0 ()5) and with the disease activity score (r=^0 824, P<0002). There were no significant changes in levels of sCD4 or sCDB. although the levels of sCD4 tended to be higher at the time of major relapses. We conclude that major relapses of Wegener's granulomatosis are accompanied by systemic T cell activation, T cell activation, however, does not appear to precede the rise in ANCA titre.

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“…While an increased CD25 expression in T cells of HD patients has been observed previously [28][29][30][31][32][33], the role of uraemia versus dialysis in this abnormality remain to be elucidated in more detail. In our study, the increased CD25 expression in CD4 + T cells was found in all uraemic patients, irrespective of dialysis modality, suggesting an influence of uraemia per se.…”

Section: Discussionmentioning

confidence: 80%

Altered CD46-mediated T cell co-stimulation in haemodialysis patients

Brinkkoetter

Marinaki

Göttmann

et al. 2005

Clinical and Experimental Immunology

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SummaryWhile most of our understanding of immune dysfunction in dialysis patients involves alterations in CD28-CD80/86 signalling, nothing is known of CD46-mediated co-stimulation of T cells in these patients. Because C3b/C4b bind to CD46 and complement activation occurs during haemodialysis (HD), we addressed whether CD46-mediated T cell activation is altered in HD ( n = 9), peritoneal dialysis (PD) ( n = 10) and predialysis patients ( n = 8) compared to healthy controls (HC) ( n = 8). T cell surface markers, T cell proliferation and interleukin (IL)-10 production were studied in CD4 + T cells. In addition, CD46 splice-variants and IL-10 promoter gene polymorphisms were studied by reverse transcription (RT) or amplification refractory mutation systempolymerase chain reaction (ARMS-PCR), respectively. In all uraemic patients, irrespective of the stage of renal insufficiency or dialysis modality, a significant increase in the percentage of CD25 positivity in naive CD4 + T cells was found (64% ± ± ± ± 21% versus 23% ± ± ± ± 18%, P < < < < 0·001). Lymphocytes of HD patients proliferated in greater numbers and produced more IL-10 after costimulation with anti-CD46 than after co-stimulation with anti-CD28. This was also found in CD4 + T cells of PD patients, albeit to a lesser extent. In contrast, with T cells of predialysis patients and of HC, co-stimulation via CD28 was more efficient. The observed alterations in T cell proliferation and IL-10 production were associated neither with CD46 splice variants nor with IL-10 promoter gene polymorphisms. Lymphocytes of HD patients show an increased response on CD46 co-stimulation. These data suggest that ongoing complement activation in HD patients may lead to alterations in acquired immunity.

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Immune Deficiency in Uremia: Interleukin-2 Production and Responsiveness and Interleukin-2 Receptor Expression and Release

Cited by 36 publications

References 26 publications

Characteristic Cytokine Products of Th1 and Th2 Cells in Hemodialysis Patients

Characteristic Cytokine Products of Th1 and Th2 Cells in Hemodialysis Patients

Serum markers of T cell activation in relapses of Wegener's granulomatosis

Altered CD46-mediated T cell co-stimulation in haemodialysis patients

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