@article{bac76f7800f94736a227b0eb8c88e53a,
title = "T cell ignorance is bliss: T cells are not tolerized by Langerhans cells presenting human papillomavirus antigens in the absence of costimulation",
abstract = "Human papillomavirus type 16 (HPV16) infections are intra-epithelial, and thus, HPV16 is known to interact with Langerhans cells (LCs), the resident epithelial antigen-presenting cells (APCs). The current paradigm for APC-mediated induction of T cell anergy is through delivery of T cell receptor signals via peptides on MHC molecules (signal 1), but without costimulation (signal 2). We previously demonstrated that LCs exposed to HPV16 in vitro present HPV antigens to T cells without costimulation, but it remained uncertain if such T cells would remain ignorant, become anergic, or in the case of CD4+ T cells, differentiate into Tregs. Here we demonstrate that Tregs were not induced by LCs presenting only signal 1, and through a series of in vitro immunizations show that CD8+ T cells receiving signal 1+2 from LCs weeks after consistently receiving signal 1 are capable of robust effector functions. Importantly, this indicates that T cells are not tolerized but instead remain ignorant to HPV, and are activated given the proper signals.",
keywords = "HPV16, Human papillomavirus, Immune tolerance, Langerhans cells, T cell anergy, T cell ignorance",
author = "Woodham, {Andrew W.} and Lisa Yan and Skeate, {Joseph G.} and {van der Veen}, Daniel and Brand, {Heike E.} and Wong, {Michael K.} and {Da Silva}, {Diane M.} and Kast, {W. Martin}",
note = "Funding Information: AWW, LY, JGS, DV, and DMD performed experiments. AWW, LY, DMD, and WMK wrote the manuscript. AWW, LY, DMD, WMK designed the study. HEB contributed materials and technical support, and MKW collected donor samples. This research was supported by Public Health Service Grant R01 CA074397 from the National Cancer Institute (to WMK). Contributions from the Netherland-American Foundation , Sammie׳s Circle and the Karl H. and Ruth M. Balz trust are also gratefully acknowledged. WMK holds the Walter A. Richter Cancer Research Chair. LY and AWW are TL1 scholars supported by SC CTSI (NIH/NCRR/NCATS) Grant # TL1TR000132 . Additional support for AWW from the ARCS Foundation John and Edith Leonis Award is greatly appreciated. Cytokine multiplex assays were run with the assistance of the USC Norris Comprehensive Cancer Center Beckman Center for Immune Monitoring. The authors would also like to thank Ella Selders, Yvonne Bogdanovich, Johannes van Tilburg, and Christine Ofiesh for additional support. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. Publisher Copyright: {\textcopyright} 2016 The Authors",
year = "2016",
month = dec,
day = "1",
doi = "10.1016/j.pvr.2016.01.002",
language = "English (US)",
volume = "2",
pages = "21--30",
journal = "Papillomavirus Research",
issn = "2405-8521",
publisher = "Elsevier BV",
}