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Killer cell immunoglobulin receptor profile on CD 4 + CD 28 − T cells and their pathogenic role in non‐dialysis‐dependent and dialysis‐dependent chronic kidney disease patients
Author(s) -
Zal Behnam,
Chitalia Nihil,
Ng Yin Sing,
Trieu Verna,
Javed Sana,
Warrington Rachelle,
Kaski Juan Carlos,
Banerjee Debasish,
Baboonian Christina
Publication year - 2015
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12429
Subject(s) - kidney disease , cd28 , dialysis , end stage renal disease , medicine , antibody , immunology , endocrinology , hemodialysis , t cell , immune system
Summary There is a progressive increase in cardiovascular disease with declining renal function, unexplained by traditional risk factors. A CD 4 + T‐cell subpopulation ( CD 4 + CD 28 − ), activated by human heat‐shock protein 60 ( hHSP 60), expands in patients with acute coronary syndrome and is associated with vascular damage. These cells exhibit cytotoxicity via expression of activating killer cell‐immunoglobulin‐like receptor KIR 2 DS 2, mainly in the absence of inhibitory KIR 2 DL 3. We investigated expansion of these cells and the pathogenic role of the KIR in non‐dialysis‐dependent chronic kidney disease ( NDD ‐ CKD ) and end‐stage haemodialysis‐dependent renal disease ( HD ‐ ESRD ) patients. CD 4 + CD 28 − cells were present in 27% of the NDD ‐ CKD and HD ‐ ESRD patients (8–11% and 10–11% of CD 4 + compartment, respectively). CD 4 + CD 28 − cells were phenotyped for KIR and DAP 12 expression. Cytotoxicity was assessed by perforin and pro‐inflammatory function by interferon‐ γ expression on CD 4 + CD 28 − clones ( NDD ‐ CKD n = 97, HD ‐ ESRD n = 262). Thirty‐four per cent of the CD 4 + CD 28 − cells from NDD ‐ CKD expressed KIR 2 DS 2 compared with 56% in HD ‐ ESRD patients ( P = 0·03). However, 20% of clones expressed KIR 2 DL 3 in NDD ‐ CKD compared with 7% in HD ‐ ESRD patients ( P = 0·004). DAP 12 expression in CD 28 − 2 DS 2 + clones was more prevalent in HD ‐ ESRD than NDD ‐ CKD (92% versus 60%; P < 0·001). Only 2 DS 2 + 2 DL 3 − DAP 12 + clones were cytotoxic in response to hHSP 60. CD 4 + CD 28 − cells exhibited increased KIR 2 DS 2, reduced KIR 2 DL 3 and increased DAP 12 expression in HD ‐ ESRD compared with NDD ‐ CKD patients. These findings suggest a gradual loss of expression, functionality and protective role of inhibitory KIR 2 DL 3 as well as increased cytotoxic potential of CD 4 + C28 − cells with progressive renal impairment. Clonal expansion of these T cells may contribute to heightened cardiovascular events in HD ‐ESRD.