Identification of the CD4(+) T cell as a major pathogenic factor in ischemic acute renal failure.
Leukocytes have been implicated in the pathogenesis of ischemic acute renal failure (ARF), but the roles of the individual cell types involved are largely unknown. Recent indirect evidence suggests that T cells may play an important role in a murine model of ARF. In the current study, we found that mice deficient in T cells (nu/nu mice) are both functionally and structurally protected from postischemic renal injury. Reconstitution of nu/nu mice with wild-type T cells restored postischemic injury. We then analyzed the contribution of the individual T cell subsets to postischemic injury and found that mice deficient in CD4(+) T cells, but not mice deficient in CD8(+) T cells, were significantly protected from ARF. Direct evidence for a pathophysiologic role of the CD4(+) T cell was obtained when reconstitution of CD4-deficient mice with wild-type CD4(+) T cells restored postischemic injury. In addition, adoptive transfers of CD4(+) T cells lacking either the costimulatory molecule CD28 or the ability to produce IFN-gamma were inadequate to restore injury phenotype. These results demonstrate that the CD4(+) T cell is an important mediator of ischemic ARF, and targeting this cell may yield novel therapies.
Burne
M J
MJ
Division of Nephrology, Hennepin County Medical Center, University of Minnesota, Minneapolis, Minnesota, USA.
Daniels
F
F
El Ghandour
A
A
Mauiyyedi
S
S
Colvin
R B
RB
O'Donnell
M P
MP
Rabb
H
H
D058186:Acute Kidney Injury / Q000209:etiology* / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D018106:CD28 Antigens / Q000096:biosynthesis; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D016827:CD8 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D009504:Neutrophils / Q000378:metabolism; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
D018106:CD28 Antigens; D015704:CD4 Antigens; D016827:CD8 Antigens; D007371:Interferon-gamma