期刊
JOURNAL OF INFECTIOUS DISEASES
卷 198, 期 2, 页码 203-212出版社
OXFORD UNIV PRESS INC
DOI: 10.1086/589510
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资金
- Intramural NIH HHS Funding Source: Medline
- Medical Research Council [G0801976, G0400802] Funding Source: Medline
- NCI NIH HHS [N01CO12400, N01-CO-12400, N01 CO012400] Funding Source: Medline
- NIAID NIH HHS [AI050798, R01 AI050798] Funding Source: Medline
- NIDA NIH HHS [R01 DA013245, R01 DA009532, R01 DA016159, R01-DA13245, R01-DA09532, R01-DA16159] Funding Source: Medline
- Medical Research Council [G9818340B, G0400802] Funding Source: researchfish
- MRC [G0400802] Funding Source: UKRI
Background. Injection drug users (IDUs) who successfully clear hepatitis C virus (HCV) have a reduced risk of developing chronic reinfection, despite their continuing exposure to the virus. To identify immunological correlates for this apparent protection, we studied HCV-specific immune responses in long-term IDUs (duration, > 10 years). Methods. HCV-specific T cell responses were assessed in proliferation, enzyme-linked immunospot (ELISPOT), interferon (IFN)-gamma secretion, and cytotoxicity assays, whereas HCV-specific antibodies were assessed in enzyme immunoassays (EIAs), chemiluminescent assays, and in vitro neutralization assays. Results. HCV-specific T cell proliferation and IFN-gamma production were more common in nonviremic EIA-positive IDUs (16[94%] of 17 IDUs) than in viremic EIA-positive IDUs (9[45%] of 20 IDUs) (P = .003). They were also noted in 16 (62%) of 26 nonviremic EIA-negative IDUs. In contrast, 19 (90%) of 21 viremic IDUs displayed neutralizing antibodies (nAbs), compared with 9 (56%) of 16 nonviremic EIA-positive IDUs ( P = .04) and 0 of 24 nonviremic EIA-negative IDUs. Nonviremic IDUs with nAbs were older ( P = .0115) than those without nAbs, but these groups did not differ in terms of either injection drug use duration or HCV-specific T cell responses. Conclusion. The reduced risk of HCV persistence in IDUs previously recovered from HCV infection correlated with T cell responses, and prolonged antigenic stimulation appears to be required to maintain humoral responses.
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