title: Identification of the CD4(+) T cell as a major pathogenic factor in ischemic acute renal failure.
abstract: 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.
authors.affiliation: Division of Nephrology, Hennepin County Medical Center, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Burne
authors.forename: F
authors.initials: F
authors.lastname: Daniels
authors.forename: A
authors.initials: A
authors.lastname: El Ghandour
authors.forename: S
authors.initials: S
authors.lastname: Mauiyyedi
authors.forename: R B
authors.initials: RB
authors.lastname: Colvin
authors.forename: M P
authors.initials: MP
authors.lastname: O'Donnell
authors.forename: H
authors.initials: H
authors.lastname: Rabb
mesh_terms: 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
chemical_list: D018106:CD28 Antigens; D015704:CD4 Antigens; D016827:CD8 Antigens; D007371:Interferon-gamma