Two Strikes and You're Out? The Pathogenic Interplay of Coinhibitor Deficiency and Lymphopenia-Induced Proliferation.

Abstract

Lymphopenia-induced proliferation (LIP) occurs when resources for T cell survival in a host are in excess. LIP has been associated with the development of inflammatory disease in situations where an additional disease-predisposing cofactor is present during LIP. This has led to the view of LIP-driven autoimmunity as a two hit model; however, not all cofactors have equal ability to precipitate autoimmunity and we have recently shown that in some circumstances, such as the absence of the coinhibitory molecule PD-1, additional hits are required. Herein we review factors controlling LIP, including coinhibitory molecules and other attenuators of TCR signaling, with a focus on their contribution to LIP-driven autoimmunity. Rather than viewing LIP-associated autoimmunity as an n-hit model, we suggest a more quantitative view of lymphopenia with respect to the factors that promote LIP as a tool to predict autoimmune potential and to inform tumor immunotherapy approaches.

• Authors: Kristofor K Ellestad, Colin C Anderson
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 198 Issue 7 Pg. 2534-2541 (04 01 2017) ISSN: 1550-6606 [Electronic] United States
• PMID: 28320914 (Publication Type: Journal Article, Review, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 by The American Association of Immunologists, Inc.

Topics

• Animals
• Autoimmunity (immunology)
• Cell Proliferation (physiology)
• Humans
• Lymphocyte Activation (immunology)
• Lymphopenia (immunology)
• T-Lymphocytes (immunology)