CD55 costimulation induces differentiation of a discrete T regulatory type 1 cell population with a stable phenotype

Unlike other helper T cells, the costimulatory ligands responsible for T regulatory type 1 (Tr1) cell differentiation remain undefined. Understanding the molecular interactions driving peripheral Tr1 differentiation is important because Tr1s potently regulate immune responses by IL-10 production. In...

Full description

Saved in:

Bibliographic Details
Published in:	The Journal of immunology (1950) Vol. 191; no. 12; pp. 5895 - 5903
Main Authors:	Sutavani, Ruhcha V, Bradley, Richard G, Ramage, Judith M, Jackson, Andrew M, Durrant, Lindy G, Spendlove, Ian
Format:	Journal Article
Language:	English
Published:	United States 15-12-2013
Subjects:	Antigens, CD - immunology Antigens, Differentiation, T-Lymphocyte - analysis CD28 Antigens - immunology CD55 Antigens - immunology Cell Division Cells, Cultured Humans Immunophenotyping Interferon-gamma - analysis Interleukin-10 - metabolism Interleukin-2 - biosynthesis Interleukin-2 - genetics Lymphocyte Activation Lymphopoiesis T-Lymphocyte Subsets - chemistry T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - metabolism T-Lymphocytes, Regulatory - chemistry T-Lymphocytes, Regulatory - classification T-Lymphocytes, Regulatory - immunology T-Lymphocytes, Regulatory - metabolism Th1 Cells - chemistry Th1 Cells - immunology Th1 Cells - metabolism
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Unlike other helper T cells, the costimulatory ligands responsible for T regulatory type 1 (Tr1) cell differentiation remain undefined. Understanding the molecular interactions driving peripheral Tr1 differentiation is important because Tr1s potently regulate immune responses by IL-10 production. In this study, we show that costimulation of human naive CD4(+) cells through CD97/CD55 interaction drives Tr1 activation, expansion, and function. T cell activation and expansion was equipotent with CD55 or CD28 costimulation; however, CD55 costimulation resulted in two IL-10-secreting populations. Most IL-10 was secreted by the minor Tr1 population (IL-10(high)IFN-γ(-)IL-4(-), <5% cells) that expresses Tr1 markers CD49b, LAG-3, and CD226. This Tr1 phenotype was not restimulated by CD28. However, on CD55 restimulation, Tr1s proliferated and maintained their differentiated IL-10(high) phenotype. The Tr1s significantly suppressed effector T cell function in an IL-10-dependent manner. The remaining (>95%) cells adopted a Th1-like IFN-γ(+) phenotype. However, in contrast to CD28-derived Th1s, CD55-derived Th1s demonstrated increased plasticity with the ability to coexpress IL-10 when restimulated through CD55 or CD28. These data identify CD55 as a novel costimulator of human Tr1s and support a role for alternative costimulatory pathways in determining the fate of the growing number of T helper populations. This study demonstrates that CD55 acts as a potent costimulator and activator of human naive CD4(+) cells, resulting in the differentiation of a discrete Tr1 population that inhibits T cell function in an IL-10-dependent manner and maintains the Tr1 phenotype upon restimulation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0022-1767 1550-6606
DOI:	10.4049/jimmunol.1301458