Role of alpha/beta and gamma/delta T cells in renal ischemia-reperfusion injury.
T cells have been implicated in the pathogenesis of renal ischemia-reperfusion injury (IRI). To date existing data about the role of the T cell receptor (Tcr) are contradictory. We hypothesize that the Tcr plays a prominent role in the late phase of renal IRI. Therefore, renal IRI was induced in alpha/beta, gamma/delta T cell-deficient and wild-type mice by clamping renal pedicles for 30 min and reperfusing for 24, 48, 72, and 120 h. Serum creatinine increased equally in all three groups 24 h after ischemia but significantly improved in Tcr-deficient animals compared with wild-type controls after 72 h. A significant reduction in renal tubular injury and infiltration of CD4+ T-cells in both Tcr-deficient mice compared with wild-type controls was detected. Infiltration of alpha/beta T cells into the kidney was reduced in gamma/delta T cell-deficient mice until 72 h after ischemia. In contrast, gamma/delta T cell infiltration was equal in wild-type and alpha/beta T cell-deficient mice, suggesting an interaction between alpha/beta and gamma/delta T cells. Data from gamma/delta T cell-deficient mice were confirmed by in vivo depletion of gamma/delta T cells in C57BL/6 mice. Whereas alpha/beta T cell-deficient mice were still protected after 120 h, gamma/delta T cell-deficient mice showed a "delayed wild-type phenotype" with a dramatic increase in kidney-infiltrating alpha/beta, Tcr-expressing CD4+ T-cells. This report provides further evidence that alpha/beta T cells are major effector cells in renal IRI, whereas gamma/delta T cells play a role as mediator cells in the first 72 h of renal IRI.
Hochegger
Kathrin
K
Clinical Division of Nephrology, Clinical Department of Internal Medicine, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria.
Schätz
Tobias
T
Eller
Philipp
P
Tagwerker
Andrea
A
Heininger
Dorothea
D
Mayer
Gert
G
Rosenkranz
Alexander R
AR
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D005786:Gene Expression Regulation; D007674:Kidney Diseases / Q000473:pathology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics* / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism*; D016176:T-Lymphocyte Subsets; D013997:Time Factors
D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta