期刊
JOURNAL OF IMMUNOLOGY
卷 186, 期 10, 页码 5854-5862出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1001024
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- National Heart, Lung, and Blood Institute [5 P50 HL074732-03]
Serial EBV load monitoring of clinically asymptomatic pediatric thoracic organ transplant patients has identified three groups of children who exhibit undetectable (< 100 copies/ml), chronic low (100-16,000 copies/ml), or chronic high (> 16,000 copies/ml) EBV loads in peripheral blood. Chronic high EBV load patients have a 45% rate of progression to late-onset posttransplant lympho-proliferative disorders. In this article, we report that asymptomatic patients carrying EBV loads (low and high) expressed increased frequencies of EBV-specific CD8(+) T cells, as compared with patients with undetectable EBV loads. Although patients with low viral load displayed EBV-specific CD8(+) T cells with moderate signs of activation (CD38(+/-)/CD127(+/-)), programmed death 1 upregulation and effective IFN-gamma secretion, high EBV load carriers showed significant CD38(+) upregulation, features of cellular exhaustion (programmed death 1(+)/CD127(-)) accompanied by a decline in IFN-gamma release. Immunopolarization of EBV-specific CD8(+) T cells was skewed from the expected type 1 (IFN-gamma) toward type 0 (IFN-gamma/IL-5) in patients, and Tr1 (IL-10) in high load carriers. These results indicate the importance of chronic EBV load and of the levels of antigenic pressure in shaping EBV-specific memory CD8(+) T cells. Concomitant phenotypic and functional EBV monitoring is critical for identifying the complex functional versus exhausted signature of EBV-specific CD8(+) T cells, with implications for immunologic monitoring in the clinic. The Journal of Immunology, 2011, 186: 5854-5862.
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