First published February 1, 2011 - More info
Having successfully developed mechanisms to evade immune clearance, hepatitis C virus (HCV) establishes persistent infection in approximately 75%–80% of patients. In these individuals, the function of HCV-specific CD8+ T cells is impaired by ligation of inhibitory receptors, the repertoire of which has expanded considerably in the past few years. We hypothesized that the coexpression of the negative regulatory receptors T cell immunoglobulin and mucin domain–containing molecule 3 (Tim-3) and programmed death 1 (PD-1) in HCV infection would identify patients at risk of developing viral persistence during and after acute HCV infection. The frequency of PD-1–Tim-3– HCV-specific CTLs greatly outnumbered PD-1+Tim-3+ CTLs in patients with acute resolving infection. Moreover, the population of PD-1+Tim-3+ T cells was enriched for within the central memory T cell subset and within the liver. Blockade of either PD-1 or Tim-3 enhanced in vitro proliferation of HCV-specific CTLs to a similar extent, whereas cytotoxicity against a hepatocyte cell line that expressed cognate HCV epitopes was increased exclusively by Tim-3 blockade. These results indicate that the coexpression of these inhibitory molecules tracks with defective T cell responses and that anatomical differences might account for lack of immune control of persistent pathogens, which suggests their manipulation may represent a rational target for novel immunotherapeutic approaches.
Rachel H. McMahan, Lucy Golden-Mason, Michael I. Nishimura, Brian J. McMahon, Michael Kemper, Todd M. Allen, David R. Gretch, Hugo R. Rosen
Original citation: J. Clin. Invest. 2010;120(12):4546–4557. doi:10.1172/JCI43127.
Citation for this corrigendum: J. Clin. Invest. 2011;121(2):821. doi:10.1172/JCI46311.
In the section of Methods titled “Antibodies and flow cytometric analysis,” the antibody clone name for the anti–Tim-3 antibody was given incorrectly. The correct sentences appear below:
Directly conjugated antibodies against the following surface molecules were used: CCR7–PE-Cy7 (clone 3D12), CD27–APC-H7 (clone M-T271), CD45RA-APC (clone HI100), CD69-FITC (clone L78), HLA-DR–PerCP (clone L243), CD45RO–PE-Cy7 (clone UCHL1), CD3–Pacific Blue (clone UCHT1), CD4-V500 (clone RPA-T4), CD8–Alexa Fluor 700 or CD8-PerCP (clone SK1), and PD-1–FITC (clone MIH4), all from BD Biosciences. The PE-conjugated antibody and the blocking antibody for Tim-3 (clone 344823) were obtained from R&D; the blocking antibody gave results that were comparable to those of 1G5 anti–Tim-3 antibody, provided by Vijay Kuchroo (Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA).
The authors regret the error.