In:
The Journal of Immunology, The American Association of Immunologists, Vol. 194, No. 1_Supplement ( 2015-05-01), p. 52.29-52.29
Abstract:
In the ESRD patients, a major cause of death is cardiovascular disease (CVD) and its pathologic processes have been suggested to link to uremia-related chronic inflammation. Although concept of ESRD-related immune dysfunction is well-accepted, little is known about how uremic toxins affect cellular immunity involved with pathogenesis of CVD in the patients. Thus, we investigated phenotypic and functional features of CD4 T cells and monocytes in the ESRD patients and their immune responses mediated by indoxyl sulfate (IS), a key uremic toxin in order to explore the pathogenic roles of these cells for vascular endothelial cells (VEC). In ESRD patients, CD4+CD28null T cells and CD16+ monocytes were expanded as compared with HC. To explore how uremic milieu affects immune responses, monocytes were stimulated with IS. These monocytes produced a large amount of TNF-α through aryl hydrocarbon receptor. TNF-α stimulated VEC greatly produced CX3CL1, a ligand of CX3CR1 which is overexpressed by CD4+CD28null T cells and CD16+ monocytes. CD4+CD28null T cells are preferentially recruited by CX3CL1 and moreover, CD4+CD28null T cells have cytotoxic capability allowing for induced apoptosis of VEC in response to TCR stimulation. Our findings suggest that IS-mediated immune dysfunction may play a critical role for development and accelerated progression of CVD through VEC damage in the ESRD patients.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.194.Supp.52.29
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2015
detail.hit.zdb_id:
1475085-5
detail.hit.zdb_id:
3056-9
