Roquin differentiates the specialized functions of duplicated T cell costimulatory receptor genes CD28 and ICOS

Michelle A Linterman; Robert J Rigby; Raphael Wong; Diego Silva; David Withers; Graham Anderson; Naresh K Verma; Robert Brink; Andreas Hutloff; Chris C Goodnow; Carola G Vinuesa

doi:10.1016/j.immuni.2008.12.015

Roquin differentiates the specialized functions of duplicated T cell costimulatory receptor genes CD28 and ICOS

Immunity. 2009 Feb 20;30(2):228-41. doi: 10.1016/j.immuni.2008.12.015. Epub 2009 Feb 12.

Authors

Michelle A Linterman¹, Robert J Rigby, Raphael Wong, Diego Silva, David Withers, Graham Anderson, Naresh K Verma, Robert Brink, Andreas Hutloff, Chris C Goodnow, Carola G Vinuesa

Affiliation

¹ Division of Immunology and Genetics, John Curtin School of Medical Research, Australian National University, Canberra, Australia.

PMID: 19217324
DOI: 10.1016/j.immuni.2008.12.015

Abstract

During evolutionary adaptation in the immune system, host defense is traded off against autoreactivity. Signals through the costimulatory receptor CD28 enable T cells to respond specifically to pathogens, whereas those through the related costimulatory receptor, ICOS, which arose by gene duplication, are critical for affinity maturation and memory antibody responses. ICOS ligand, unlike the pathogen-inducible CD28 ligands, is widely and constitutively expressed in the immune system. Here, we show that crosstalk between these two pathways provides a mechanism for obviating the normal T cell dependence on CD28. Several CD28-mediated responses-generation of follicular helper T cells, germinal center formation, T helper 1 cell-dependent extrafollicular antibody responses to Salmonella and bacterial clearance, and regulatory T cell homeostasis-became independent of CD28 and dependent on ICOS when the E3 ubiquitin ligase Roquin was mutated. Mechanisms to functionally compartmentalize ICOS and CD28 signals are thus critical for two-signal control of normal immune reactions.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alleles
Animals
Antigens, Differentiation, T-Lymphocyte / genetics
Antigens, Differentiation, T-Lymphocyte / immunology*
Antigens, Differentiation, T-Lymphocyte / metabolism
CD28 Antigens / genetics
CD28 Antigens / immunology*
CD28 Antigens / metabolism
Cell Differentiation / immunology
Gene Expression Regulation
Germinal Center / immunology
Immunologic Memory / immunology
Inducible T-Cell Co-Stimulator Protein
Interleukin-2 / immunology
Interleukin-2 / metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Mutation / genetics
Salmonella / immunology
Signal Transduction / immunology
T-Lymphocytes / cytology
T-Lymphocytes / immunology*
T-Lymphocytes / metabolism
Thymus Gland / cytology
Thymus Gland / immunology
Ubiquitin-Protein Ligases / genetics
Ubiquitin-Protein Ligases / immunology*
Ubiquitin-Protein Ligases / metabolism

Substances

Antigens, Differentiation, T-Lymphocyte
CD28 Antigens
Icos protein, mouse
Inducible T-Cell Co-Stimulator Protein
Interleukin-2
Rc3h1 protein, mouse
Ubiquitin-Protein Ligases