Role of the T-cell receptor in kidney ischemia-reperfusion injury.
T cells have been demonstrated to modulate ischemia-reperfusion injury (IRI) in kidney, lung, liver and intestine. The underlying mechanisms for T-cell engagement in IRI are unknown. We hypothesized that the T-cell receptor (TCR) plays a role in renal IRI, and examined the effects of TCR alpha/beta (alphabeta) and gamma/delta (gammadelta) deficiency on ischemic acute renal failure (ARF). TCR-specific deficiency in specific mice was confirmed by fluorescence-activated cell sorting analysis using monoclonal antibodies (Abs). IRI was induced by bilateral clamping of kidney pedicles for 30 min, followed by reperfusion. Serum creatinine and kidney histopathology were used to assess the severity of experimental ARF. TCR alphabeta-deficient mice were significantly protected from kidney dysfunction compared to wild-type (WT) littermates after IRI (P<0.05). Histologic analysis demonstrated a significant reduction in renal tubular injury in both TCR alphabeta- and gammadelta-deficient mice compared to WT mice postischemia. TCR alphabeta-deficient mice had reduced tumor necrosis factor-alpha and interleukin-6 protein expression in kidney tissue compared to WT mice at 24 h postischemia using a microbead-based protein detection platform. Relative protection from kidney IRI did not correlate with neutrophil and macrophage infiltration of kidney tissue. Thus, the TCR plays a direct but modest pathophysiological role in kidney IRI. These data suggest that alloantigen-independent activation in IRI can lead to engagement of antigen-specific molecules on T cells. Furthermore, given that the TCR is already a target for diagnostics and therapeutic strategies in immune diseases, these approaches can now be harnessed for IRI.
Savransky
V
V
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Molls
R R
RR
Burne-Taney
M
M
Chien
C-C
CC
Racusen
L
L
Rabb
H
H
D000818:Animals; D007376:Interleukin-2 / Q000096:biosynthesis; D007668:Kidney / Q000098:blood supply* / Q000276:immunology / Q000473:pathology; D051379:Mice; D020556:Neutrophil Infiltration; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015427:Reperfusion Injury / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D013601:T-Lymphocytes / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D014409:Tumor Necrosis Factor-alpha