CD28 down-regulation on CD4 T cells is a marker for graft dysfunction in lung transplant recipients.
Am J Respir Crit Care Med
; 178(7): 765-73, 2008 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-18617642
ABSTRACT
RATIONALE Repeated antigen-driven proliferations cause CD28 on T cells to down-regulate. We hypothesized that alloantigen-induced proliferations could cause CD28 down-regulation in lung transplant recipients. OBJECTIVES:
To ascertain if CD28 down-regulation on CD4 T cells associated with manifestations of allograft dysfunction in lung transplant recipients.METHODS:
Peripheral blood CD4 T cells from 65 recipients were analyzed by flow cytometry, cytokine multiplex and proliferative assays, and correlated with clinical events. MEASUREMENTS AND MAINRESULTS:
Findings that CD28 was present on less than 90% of total CD4 T cells were predominantly seen among the recipients with bronchiolitis obliterans syndrome (specificity = 88%). Perforin and granzyme B were produced by >50% of the CD4(+)CD28(null) cells, but less than 6% of autologous CD4(+)CD28(+) cells (P < 0.006). CD4(+)CD28(null) cells also had increased productions of proinflammatory cytokines, but less frequently expressed regulatory T-cell marker FoxP3 (2.1 +/- 1.3%), compared with autologous CD4(+)CD28(+) (9.5 +/- 1.4; P = 0.01). Cyclosporine A (100 ng/ml) inhibited proliferation of CD4(+)CD28(null) cells by 33 +/- 11% versus 68 +/- 12% inhibition of CD4(+)CD28(+) (P = 0.025). FEV(1) fell 6 months later (0.35 +/- 0.04 L) in recipients with CD4(+)CD28(+)/CD4(total) less than 90% (CD28% Low) compared with 0.08 +/- 0.08 L among CD4(+)CD28(+)/CD4(total) (CD28% High) greater than 90% (CD28% High) recipients (P = 0.013). Two-year freedom from death or retransplantation in CD28% Low recipients was 32 +/- 10% versus 78 +/- 6% among the CD28% High subjects (P < 0.0001).CONCLUSIONS:
CD28 down-regulation on CD4 cells is associated with bronchiolitis obliterans syndrome and poor outcomes in lung transplantation recipients. CD4(+)CD28(null) cells have unusual, potentially pathogenic characteristics, and could be important in the progression of allograft dysfunction. These findings may illuminate a novel paradigm of transplantation immunopathogenesis, and suggest that CD28 measurements could identify recipients at risk for clinical deteriorations.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bronquiolite Obliterante
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Linfócitos T CD4-Positivos
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Subpopulações de Linfócitos
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Antígenos CD28
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Rejeição de Enxerto
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article