Regulatory interactions of alphabeta and gammadelta T cells in glomerulonephritis.

Abstract:

BACKGROUND:Several lines of evidence suggest that cellular immune mechanisms contribute to glomerulonephritis. METHODS:The roles of alphabeta and gammadelta T cells in the pathogenesis of glomerulonephritis were investigated in a model of nephrotoxic nephritis in mice deficient in either T-cell population [T-cell receptor (TCR)beta and TCRdelta knockout mice]. The model, induced by the injection of rabbit anti-mouse glomerular basement membrane antibody, is characterized by the development of proteinuria and glomerular damage over a 21-day observation period in wild-type mice. RESULTS:Mice deficient in either alphabeta or gammadelta T cells developed minimal proteinuria and glomerular lesions and had a significant reduction in macrophage accumulation compared with wild-type mice. In gammadelta T-cell-deficient mice, circulating levels and glomerular deposition of autologous IgG were comparable to wild-type levels, while alphabeta T-cell-deficient mice had no autologous IgG production. Autologous antibody production was not required for the development of glomerulonephritis since mice that lack IgG and B cells (micro-chain-/-) developed similar proteinuria to that observed in wild-type mice. CONCLUSIONS:These studies suggest a proinflammatory role for both alphabeta and gammadelta T cells in glomerular injury, independent of the humoral response. This is the first demonstration, to our knowledge, that both T-cell subsets contribute to the progression of a disease, and it suggests that complex regulatory interactions between alphabeta and gammadelta T cells play a role in glomerular injury.

journal_name

Kidney Int

journal_title

Kidney international

authors

Rosenkranz AR,Knight S,Sethi S,Alexander SI,Cotran RS,Mayadas TN

doi

10.1046/j.1523-1755.2000.00263.x

subject

Has Abstract

pub_date

2000-09-01 00:00:00

pages

1055-66

issue

3

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(15)47197-2

journal_volume

58

pub_type

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