The effect of uremia and transplantation on lymphocyte subpopulations

Quadracci, Leonard J.; Ringdén, Olle; Krzymański, M

doi:10.1038/ki.1976.93

Cited by 78 publications

(36 citation statements)

References 16 publications

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“…To this end, purified T lymphocytes were obtained from patients 2 (NR), 4 (NR), 17 To further exclude that reduced IL-2 production was indeed not due to a defect at the T cell level we investigated, in addition, the proliferative responses of T lymphocytes to triggering via the "alternative pathway" of T cell activation (5). Although this pathway is engaged via a T cell antigen-receptor unrelated glycoprotein (T I 1), proliferation is dependent on an intact IL-2/IL-2 receptor system as well.…”

Section: Resultsmentioning

confidence: 99%

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Selective blockade of the antigen-receptor-mediated pathway of T cell activation in patients with impaired primary immune responses.

Meuer¹,

Hauer²,

Kurz³

et al. 1987

J. Clin. Invest.

140

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We investigated impaired cellular immune responses of individuals on chronic hemodialysis by using monoclonal antibodies that trigger differential pathways of T cell activation. Reduced cellular reactivity, which exists in a high proportion of such patients, can be attributed to a failure of the monocyte population to support the process of primary T cell activation in vitro. This defect results in a lack of interleukin 2 production, which is critically dependent on a monocyte-derived signal. In contrast, T lymphocyte function was found to be physiologic. Perhaps more important, the degree of monocyte dysfunction in vitro correlated with the same patients' in vivo responses to hepatitis B vaccination. Addition of recombinant human interleukin 2 fully reconstituted their deficient immune response in vitro.

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Section: Resultsmentioning

confidence: 99%

“…Seroconversion occurred 12 mo after standard vaccination; anti-HBs positivity in two consecutive control patients (13,(16)(17)(18)(19)(20)(21)(22)(23)(24).…”

Section: Introductionmentioning

confidence: 99%

Selective blockade of the antigen-receptor-mediated pathway of T cell activation in patients with impaired primary immune responses.

Meuer¹,

Hauer²,

Kurz³

et al. 1987

J. Clin. Invest.

140

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

150

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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“…Although studies on hemodialysis patients point to Epo effects on immune responses, the mechanisms underlying this effect cannot be deduced under these conditions. It should be emphasized that the aforementioned studies were carried out in patients who exhibited a range of immune system abnormalities, such as impaired T cell-associated activities [42][43][44], decreased antibody response [45], increased susceptibility to infections [46] and high levels of proinflammatory cytokines [47]. Accordingly, the effects of Epo on immunological functions in hemodialysis patients are likely to be influenced by other physiological parameters, in addition to Epo administration.…”

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confidence: 99%

Erythropoietin enhances immune responses in mice

et al. 2007

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Erythropoietin (Epo) is the main erythropoietic hormone. Recombinant human Epo (rHuEpo) is thus used in clinical practice for the treatment of anemia. Accumulating data reveals that Epo exerts pleiotropic activities. We have previously shown an antineoplastic activity of Epo in murine multiple myeloma (MM) models, and in MM patients. Our findings that this anti-neoplastic effect operates via CD8 + T lymphocytes led us to hypothesize that Epo possesses a wider range of immunomodulatory functions. Here we demonstrate the effect of Epo on B lymphocyte responses, focusing on three experimental models: (i) tumor-bearing mice, (5T2 MM mouse); (ii) antigen-injected healthy mice; and (iii) antigen-injected transgenic mice (tg6), overexpressing human Epo. In the MM model, despite bone marrow dysfunction, Epo-treated mice retained higher levels of endogenous polyclonal immunoglobulins, compared to their untreated controls. In both Epo-treated wild type and tg6 mice, Epo effect was manifested in the higher levels of splenocyte proliferative response induced in vitro by lipopolysaccharide. Furthermore, these mice had increased in vivo production of anti-dinitrophenyl (DNP) antibodies following immunization with DNP-keyhole limpet hemocyanin. Epo-treated mice showed an enhanced immune response also to the clinically relevant hepatitis B surface antigen. These findings suggest a potential novel use of rHuEpo as an immunomodulator.See accompanying commentary: http://dx.doi. org/10.1002/eji.200737401 Introduction Erythropoietin (Epo), produced mainly in the adult kidney, is the major growth regulator of the erythroid cell lineage. Cloning of the Epo gene has led to the introduction of recombinant human Epo (rHuEpo) into clinical practice as a treatment for various anemias, including anemia related to chronic kidney disease and certain forms of cancer [1, 2]. Detection of the target receptor for Epo (EpoR) in cells other than erythroid progenitors, such as polymorphonuclear leukocytes, megakaryocytes, endothelial, myocardial and neural cells [3][4][5][6][7], suggests that Epo has other biological functions beyond erythropoiesis, and may have further potential therapeutic applications. These effects include improvement in congestive heart failure [8,9] and neuroprotection [10][11][12][13][14][15][16][17].* These authors contributed equally to this study. The idea that rHuEpo may have an important effect on the immune system, including both cellular and humoral type responses, derives from several lines of data, as recently reviewed [18]. For instance, clinical observations revealed that treatment with rHuEpo was associated with enhanced antibody production in hemodialysis patients, demonstrated for T cell-dependent antigens, such as tetanus toxoid and hepatitis B [19][20][21][22] as well as for the T cell-independent pneumococcal polysaccharide antigen [20]. Others have demonstrated enhancement of basal and mitogen-stimulated immunoglobulin production by cultured peripheral mononuclear cells (MNC) of dialysis patients treated ...

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The effect of uremia and transplantation on lymphocyte subpopulations

Cited by 78 publications

References 16 publications

Selective blockade of the antigen-receptor-mediated pathway of T cell activation in patients with impaired primary immune responses.

Selective blockade of the antigen-receptor-mediated pathway of T cell activation in patients with impaired primary immune responses.

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

Erythropoietin enhances immune responses in mice

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