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NDT Advance Access originally published online on April 23, 2007
Nephrology Dialysis Transplantation 2007 22(9):2540-2548; doi:10.1093/ndt/gfm228
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© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

T-cell homing receptor expression in IgA nephropathy

Arvind Batra, Alice C. Smith, John Feehally and Jonathan Barratt

Department of Infection, Immunity and Inflammation, University of Leicester, John Walls Renal Unit, Leicester General Hospital, Leicester LE5 4PW, UK

Correspondence and offprint requests to: Dr Jonathan Barratt, John Walls Renal Unit, Leicester General Hospital, Leicester LE5 4PW, UK. Email: jb81{at}le.ac.uk



  Abstract

Background. IgA nephropathy (IgAN) is characterized by mesangial deposition of polymeric IgA (pIgA). In IgAN, mucosal pIgA production is reduced while systemic production is increased, making the latter the likely source of mesangial pIgA, and suggesting a displacement of pIgA-producing cells from mucosal to systemic sites. Upon activation, lymphocytes migrate through the circulation up-regulating homing receptors (HR) which direct their return to appropriate effector locations. We investigated the HR expression of T-cell subsets in IgAN, healthy adults and membranous nephropathy (MN).

Methods. Peripheral blood cells were labelled for CD3, CD4 and CD8, and for L-selectin (naive cells), integrin {alpha}4ß1 (systemically homing cells) and integrin {alpha}4ß7 (mucosally homing cells) and analysed by flow immunocytometry.

Results. In IgAN, CD3 T cells displayed reduced L-selectin and increased {alpha}4ß1hi expression, with no difference in {alpha}4ß7. No abnormality of T-cell HR expression was found in MN. Both IgAN and healthy adults maintained their patterns of T-cell HR expression when studied again at a later time point, and the changes in IgAN were entirely accounted for by the CD4 T-cell subset with CD8 HR expression being normal.

Conclusions. The consistently reduced L-selectin expression by CD4 T cells indicates increased activation of this subset in IgAN. These activated cells express {alpha}4ß1 rather than {alpha}4ß7, and therefore home to systemic effector sites. CD4 T cells regulate antibody production, including IgA. As pIgA is overproduced in systemic sites in IgAN, we hypothesize that these activated systemic homing CD4 T cells may direct the aberrant systemic pIgA production observed in IgAN.

Keywords: IgA nephropathy; {alpha}-4 integrins; lymphocyte homing; pathogenesis; T cell

Received for publication: 19.12.06
Accepted in revised form: 23. 3.07


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