T cells activate the tumor necrosis factor-alpha system during hemodialysis, resulting in tachyphylaxis

Riemsdijk, I. C. van; Baan, Carla C.; Loonen, E. H. M.; Knoop, C. J.; Betônico, Gustavo Navarro; Niesters, Hubert G. M.; Zietse, Robert; Weimar, Willem

doi:10.1046/j.1523-1755.2001.00571.x

Cited by 9 publications

(14 citation statements)

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“…This also explains the relation found between anti-HBsAg titer and HBsAg-specific T cell proliferation. Consistent with our previous findings, 29 we observed normal polyclonal T cell proliferation in patients with ESRD, indicating no intrinsic defect in proliferative capacity.…”

Section: Discussionsupporting

confidence: 93%

Impaired Immune Responses and Antigen-Specific Memory CD4+ T Cells in Hemodialysis Patients

Litjens¹,

Huisman²,

Dorpel³

et al. 2008

Journal of the American Society of Nephrology

151

113

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Serologic responses to T cell-dependent vaccinations are severely attenuated in patients with ESRD, but the reasons for this is unknown. In this study, a detailed analysis of antigen-specific T cell responses was performed. Patients on hemodialysis and age-and gender-matched healthy control subjects were vaccinated with hepatitis B surface antigen (HBsAg), antigen-specific CD4 ϩ T cells were monitored at regular intervals with intracellular cytokine staining and proliferation assays. IL-2-and IFN-␥-producing CD4 ϩ T cells were identified as either central or effector memory CD4 ϩ T cells using antibodies directed against CD45RO and the chemokine receptor CCR7. Control subjects mounted a memory T cell response comprising both central and effector memory CD4 ϩ T cells, with the central memory response occurring 1 wk before the effector memory response. IL-2 ϩ HBsAg-specific memory CD4 ϩ T cells were primarily detected within the effector population. Patients with ESRD showed a delayed response of IL-2-and IFN-␥-producing central memory CD4 ϩ T cells, but their maximal responses were similar to those of control subjects. In contrast, patients with ESRD produced only 6.3% of the IL-2 ϩ HBsAgspecific effector memory CD4 ϩ T cells produced by control subjects (0.5 Ϯ 0.2 ϫ 10 4 /L versus 8 Ϯ 3.5 ϫ 10 4 /L; P Ͻ 0.001), and this impaired response correlated with antigen-specific T cell proliferation and anti-HBsAg IgG titers. In conclusion, the production of antigen-specific effector memory CD4 ϩ T cells after vaccination, which is critical to achieve an adequate humoral response, is severely impaired in patients with ESRD. 19: 148319: -149019: , 200819: . doi: 10.1681 Patients with ESRD show clinical signs of an immune defect characterized by an increased susceptibility for infections and a decreased immune response to T cell-dependent antigens (e.g., hepatitis B vaccination). The precise mechanisms responsible for this immune defect are unknown; however, changes in T cell subsets and/or function may contribute substantially to the impaired cellular immune response, because ESRD is associated with lymphopenia occurring in the B and T lymphocyte compartment. [1][2][3] The available data on B cell function of patients with ESRD do not indicate an impaired function. 4 The functional data on peripheral T cells in patients with ESRD are conflicting and obtained by using the unfractionated bulk of circulating T cells. 1,3,5,6 Developments in T cell research and availability of various chemokine receptors, such as CCR7, have enabled a dissection of the T lymphocytes in different subsets. 7,8 The major T cell compartments that can be distinguished are the naive T cells (Tnaive; antigen inexperienced) and the antigen ex- J Am Soc Nephrol

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Section: Discussionsupporting

confidence: 93%

Impaired Immune Responses and Antigen-Specific Memory CD4+ T Cells in Hemodialysis Patients

Litjens¹,

Huisman²,

Dorpel³

et al. 2008

Journal of the American Society of Nephrology

151

113

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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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“…In these patients the IL-2 mRNA and PHA-stimulated IL-2 production were comparable to those of healthy controls. We postulated a tachyphylactic state of T cells concerning the TNF-· production, probably a consequence of continuous stimulation by blood-membrane contact or subclinical infections without an intrinsic T cell defect [25]. Girndt et al [11] described a possible defect in the costimulatory pathways.…”

Section: Discussionmentioning

confidence: 95%

“…From these data we conclude that in patients on chronic HD no intrinsic T cell defect in vitro is present, but the tachyphylactic state for TNF-· production by uremic T cells results in a lower cytokine-driven proliferation capacity in vivo. Another confounding factor is the uremic environment [25]. This environment may strongly influence the function of T cells.…”

Section: Discussionmentioning

confidence: 99%

“…In previous studies we found a significantly lower PHAstimulated TNF-· production by T cells despite an overall activated TNF-· system. We concluded that the T cells were tachyphylactic for their TNF-· production, but could otherwise be intrinsically normal [25]. To test this hypothesis we analyzed the proliferation of peripheral blood mononuclear cells (PBMCs) as a reflection of T cell proliferation, derived from chronic HD patients upon stimulation with recombinant IL-2, IL-15 and TNF-·, and various combinations of these cytokines.…”

Section: Introductionmentioning

confidence: 99%

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Patients on Chronic Hemodialysis Have No Intrinsic Lymphocyte Defect upon Stimulation with Interleukin-2, Interleukin-15 or Tumor Necrosis Factor-Alpha

Riemsdijk

Baan²,

Loonen³

et al. 2003

Blood Purif

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Background: Patients on chronic hemodialysis (HD) suffer from general immune incompetence, resulting in a high incidence of infectious complications, impaired response to vaccinations and a high incidence of malignancy. Although various abnormalities in T cell function of HD patients have been described, it remains unclear whether this is due to an intrinsic T cell defect. Aim: In the present study we tested the capacity of T cells to proliferate upon stimulation with antigen-presenting cell and T-cell-derived cytokines. Methods: The proliferation capacity of lymphocytes obtained from patients on HD and healthy controls was determined by measuring the proliferation of peripheral blood mononuclear cells (PBMC) after stimulation with rhIL-2, rhIL-15, rhTNF-α, or combination of those cytokines. In all samples the percentage of α/β TCR-positive T cells was measured. Results: After isolation of PBMC the percentage of T cells varied from 70% (before stimulation) to 80% (after stimulation). IL-2, IL-15 and TNF-α all induced PBMC proliferation, while the combination TNF-α plus IL-2 or TNF-α plus IL-15 appeared to be additive. No difference between PBMC from HD patients and controls was found. Conclusion: We conclude that lymphocytes from HD patients have no intrinsic defects in their proliferation capacity after stimulation with IL-2, IL-15 or TNF-α, in vitro, as the increase in counts per minute is predominant.

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T cells activate the tumor necrosis factor-alpha system during hemodialysis, resulting in tachyphylaxis

Cited by 9 publications

References 0 publications

Impaired Immune Responses and Antigen-Specific Memory CD4+ T Cells in Hemodialysis Patients

Impaired Immune Responses and Antigen-Specific Memory CD4+ T Cells in Hemodialysis Patients

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

Patients on Chronic Hemodialysis Have No Intrinsic Lymphocyte Defect upon Stimulation with Interleukin-2, Interleukin-15 or Tumor Necrosis Factor-Alpha

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