TCF1 expression marks self-renewing human CD8+ T cells.

Expression of the transcription factor T-cell factor 1 (TCF1) identifies antigen-experienced murine CD8+ T cells that retain potential for lymphoid recirculation and the ability to self-renew while producing more differentiated effector cells. We found that CD8+ T cells in the blood of both healthy and chronically infected humans expressed TCF1 at 3 distinct levels: high (TCF1-hi), intermediate (TCF1-int), and low (TCF1-lo). TCF1-hi cells could be found within both the naive and memory compartments and were characterized by relative quiescence and lack of immediate effector function. A substantial fraction of TCF1-int cells were found among memory cells, and TCF1-int cells exhibited robust immediate effector functions. TCF1-lo cells were most enriched in effector memory cells that expressed the senescence marker CD57. Following reactivation, TCF1-hi cells gave rise to TCF1-lo descendants while self-renewing the TCF1-hi progenitor. By contrast, reactivation of TCF1-lo cells produced more TCF1-lo cells without evidence of de-differentiating into TCF1-hi cells. Flow cytometric analyses of TCF1 expression from patient specimens may become a useful biomarker for adaptive immune function in response to vaccination, infection, autoimmunity, and cancer.

Interferon-alpha-2b and ribavirin for retreatment of chronic hepatitis C.

BACKGROUND/AIMS: Subjects with chronic hepatitis C who fail treatment with interferon-alpha are generally divided into two groups: "relapsers" who normalized serum aminotransferase activity and have undetectable viral RNA during treatment and "non-responders" who do not achieve these results. The aim of this study was to examine retreatment of such subjects. METHODOLOGY: We studied 117 subjects with chronic hepatitis C who failed treatment with interferon-alpha, 87 of whom were "non-responders" and 30 "relapsers." Retreatment was with either interferon-alpha-2b plus ribavirin for 48 weeks or with interferon-alpha-2b plus placebo for 24 weeks followed by 24 weeks of combined therapy. RESULTS: Sustained response rates, defined as undetectable viral RNA in serum 6 months after retreatment, were 53% in "relapsers" and 10% in "non-responders" (P < 0.005). There was no significant difference if ribavirin was given for 24 or 48 weeks. In "non-responders" infected with genotypes other than type 1, 42% achieved a sustained response compared to 5% infected with genotype 1 (P = 0.027; odds ratio 7.09). CONCLUSIONS: Treatment with interferon-alpha-2b plus ribavirin is effective in approximately 50% of "relapsers" and "non-responders" infected with non-type 1 genotypes of hepatitis C virus. This therapy is only marginally effective in "non-responders" infected with genotype 1a or 1b.