S1 in the supplemental material). PBMC of Chinese patients were stimulated with the HBVgenB peptide panel, while Caucasian patients were stimulated with HBVgenD peptides. Consistent with previous data, obtained mainly for Caucasian patients (7, 9), inhibitor purchase HBV-specific T-cell responses were detected ex vivo only in patients with acute HBV infection (6/6 Chinese and 4/4 Caucasian subjects). Responses in chronic patients (18% [5/27] of Chinese and 15% [5/33] of all Caucasian individuals) were rarely observed ex vivo (Fig. 1a and b), indicating that clinical status was a stronger predictor of detectable responses than ethnicity or infecting genotype. In line with previous results (45), the envelope-specific T-cell response appears to be the only weak response detectable ex vivo in chronic HBV patients with a high HBV load (Fig.

(Fig.1b1b). FIG. 1. Ex vivo quantitative profile of HBV-specific T cells in Chinese and Caucasian HBV patients. (a) Overlapping peptide pools were used to stimulate PBMC directly ex vivo in the IFN-�� ELISPOT assay. Results from selected acute and chronic Chinese … HBV-specific T-cell responses were also compared after in vitro expansion in 17 HBVgenB-infected Chinese and 15 HBVgenD-infected Caucasian subjects. HBV-specific T-cell frequency was generally low directly ex vivo but became clearly detectable in all acute patients after in vitro expansion (Fig. (Fig.2a),2a), while such expansion was defective in chronic patients irrespective of ethnicity and HBV genotype (Fig. (Fig.2b).2b). The data for all patients are summarized in Fig. Fig.

2c,2c, which provides a comparison of the numbers of peptide mixtures able to elicit ELISPOT assay responses in acute versus chronic HBV patients. We observed the same general pattern of efficient expansion and multispecific T-cell responses in acute patients compared to weak and narrower T-cell responses in chronic patients, irrespective of ethnicities and HBV genotypes. Furthermore, previous reports suggested that Carfilzomib the magnitude of the HBV-specific T-cell response is inversely correlated with the serum HBV DNA level (7, 45); however, this relationship was not observed in our data, and there was no correlation between HBV-specific T-cell expansion and HBeAg/anti-HBe status, which is probably attributable to the limited sample size (data not shown). FIG. 2. Quantification of HBV-specific T cells after in vitro expansion. (a and b) ELISPOT analysis was performed on PBMC directly ex vivo (top panels) and after 10 days of in vitro expansion (bottom panels) using the same pools of peptides. Results from two … Functional defects of HBV-specific T cells from chronic patients.