Role of the eosinophil in chronic vascular rejection of renal allografts

Nolan, Charles R.; Saenz, Kristin P.; Thomas, Charles A.; Murphy, Kim

doi:10.1016/0272-6386(95)90601-0

Cited by 37 publications

(28 citation statements)

References 23 publications

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“…This effect of anti-IL-4 treatment has been described in several previous reports that showed that tissue eosinophilia was dependent on the presence of IL-4 (30,44) or IL-5 (45). Eosinophils have also been detected during allograft rejection in both experimental models and clinical transplantation (46,47). The vascular lesions seen in CD8 ϩ T cell-depleted CD40 Ϫ/Ϫ recipients are consistent with the ability of activated eosinophils to induce fibrotic lesions in several chronic inflammatory diseases (48,49), probably by secreting a large number of cytotoxic mediators such as eosinophil cationic proteins and activated oxygen radicals (48).…”

Section: Discussionsupporting

confidence: 58%

Critical Role for IL-4 in the Development of Transplant Arteriosclerosis in the Absence of CD40-CD154 Costimulation

Ensminger

Spriewald

Sorensen

et al. 2001

The Journal of Immunology

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Blockade of the CD40-CD154 pathway can inhibit CD4+ T cell activation but is unable to prevent immune responses mediated by CD8+ T cells. However, even in the absence of CD8+ T cells, inhibition of the CD40-CD154 pathway is insufficient to prevent the development of transplant arteriosclerosis. This study investigated the mechanisms of transplant arteriosclerosis in the absence of the CD40 pathway. C57BL/6 CD40−/− (H2b) recipients were transplanted with MHC-mismatched BALB/c (H2d) aortas. Transplant arteriosclerosis was evident in both CD40−/− and CD40+/− mice (intimal proliferation was 59 ± 5% for CD40−/− mice vs 58 ± 4% for CD40+/− mice) in the presence or absence of CD8+ T cells (intimal proliferation was 46 ± 7% for CD40−/− anti-CD8-treated mice vs 50 ± 10% for CD40+/− anti-CD8-treated mice), confirming that CD8+ T cells are not essential effector cells for the development of this disease. In CD40−/− recipients depleted of CD8+ T cells, the number of eosinophils infiltrating the graft was markedly increased (109 ± 24 eosinophils/grid for CD40−/− anti-CD8-treated mice vs 28 ± 7 for CD40+/− anti-CD8-treated mice). The increased presence of eosinophils correlated with augmented intragraft production of IL-4. To test the hypothesis that IL-4 was responsible for the intimal proliferation, CD8 T cell-depleted CD40−/− recipients were treated with anti-IL-4 mAb. This resulted in significantly reduced eosinophil infiltration into the graft (12 ± 5 eosinophils/grid for CD40−/− anti-CD8+, anti-IL-4-treated mice vs 109 ± 24 for CD40−/− anti-CD8-treated mice), intragraft eotaxin, CCR3 mRNA production, and the level of intimal proliferation (18 ± 5% for CD40−/− anti-CD8+-, anti-IL-4-treated mice vs 46 ± 7% for CD40−/− anti-CD8-treated mice). In conclusion, elevated intragraft IL-4 production results in an eosinophil infiltrate and is an important mechanism for CD8+ T cell-independent transplant arteriosclerosis in the absence of CD40-CD154 costimulation.

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Section: Discussionsupporting

confidence: 58%

Critical Role for IL-4 in the Development of Transplant Arteriosclerosis in the Absence of CD40-CD154 Costimulation

Ensminger

Spriewald

Sorensen

et al. 2001

The Journal of Immunology

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“…29,31,60 In the only report that shows the prognostic value of eosinophils in acute cellular rejection in liver transplant recipients, Ben-Ari et al 6 found that 7 of 17 patients with steroid-resistant acute rejection had high eosinophil counts before OKT3 therapy, and this subgroup had a worse clinical course requiring additional courses of steroids or FK 506 or developed chronic rejection, compared with those with normal or low eosinophil counts before OKT3 therapy. Interestingly, Nolan et al 61 suggested a role for eosinophils in the pathogenesis of chronic vascular rejection of renal allografts by staining them with an epifluorescence technique. Foster et al 62 described a continuously decreasing average eosinophil count in the graft that predicted a successful treatment of rejection with a sensitivity of 95% and a specificity of 90%.…”

Section: The Prognostic Role Of Eosinophilsmentioning

confidence: 99%

Eosinophils in acute cellular rejection in liver allografts

et al. 1998

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Eosinophils have a role in various allergic and inflammatory disease processes and participate in the process of acute rejection in solid organ allografts. Initial studies described the diagnostic value of eosinophils in kidney allograft rejection. Graft eosinophilia is a sensitive and specific marker of acute rejection in liver allografts and has been incorporated as one of the diagnostic criteria of acute rejection by the Royal Free Hospital scoring system. Blood eosinophilia also has been investigated and is a useful diagnostic marker of acute rejection in liver and kidney allografts, although studies differ in defining the day of onset of eosinophilia in relation to rejection. Eosinophils probably act through the chemokines interleukin-5 and RANTES (regulated on activation, normal T cells expressed and secreted) in the pathogenesis of acute rejection. Basic cytotoxic proteins, such as eosinophil cationic protein and major basic protein, are released by the eosinophils, and their effector role in acute rejection has been studied through the use of specific monoclonal antibodies. Successful treatment of acute rejection with corticosteroids has been associated with a decrease in graft and blood eosinophil counts. Eosinophils also act as prognostic markers of acute rejection, as shown by studies reporting that patients with elevated eosinophil counts and steroid-resistant rejection showed a worse prognosis. Further research into the effector mechanisms of eosinophils in acute rejection needs to be performed. The ability of eosinophils to distinguish those diseases with different responses to standard immunosuppression and other diseases in the context of acute rejection also needs to be studied.

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“…The observation that eosinophils and IL-5 may be present during rejection of tissue allografts has been made by several investigators in both experimental animals and humans (47,(50)(51)(52)(53)(54)(55). Whether their presence is merely secondary, or whether eosinophils play a causative role in the rejection process, has not yet been elucidated.…”

mentioning

confidence: 99%

Critical roles for IL-4, IL-5, and eosinophils in chronic skin allograft rejection

Moine¹,

Flamand²,

Demoor³

et al. 1999

J. Clin. Invest.

105

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MethodsMice. C57BL/6 and BALB/c mice were obtained from Harlan (Zeist, the Netherlands). C57BL/6.CH-2 bm12 (bm12) mice were obtained from The Jackson Laboratory (Bar Harbor, Maine, USA). C57BL/6 IL-5 knockout mice (23) were kindly provided by M. Kopf (Basel Institute for Immunology, Basel, Switzerland).Antibodies. The hamster anti-mouse CD3 mAb 145-2C11, the IgG1 rat anti-mouse IL-5 mAb TRFK-5, the IgG1 rat antimouse IL-4 mAb 11B11, and the IgG1 rat anti-mouse IL-10

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Role of the eosinophil in chronic vascular rejection of renal allografts

Cited by 37 publications

References 23 publications

Critical Role for IL-4 in the Development of Transplant Arteriosclerosis in the Absence of CD40-CD154 Costimulation

Critical Role for IL-4 in the Development of Transplant Arteriosclerosis in the Absence of CD40-CD154 Costimulation

Eosinophils in acute cellular rejection in liver allografts

Critical roles for IL-4, IL-5, and eosinophils in chronic skin allograft rejection

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