Activation of human CD4+ cells with CD3 and CD46 induces a T-regulatory cell 1 phenotype

Claudia Kemper, Andrew C. Chan, Jonathan M. Green, Kelly A. Brett, Kenneth M. Murphy and John P. Atkinson ()
Additional contact information
Claudia Kemper: Washington University School of Medicine
Andrew C. Chan: Genentech, Inc.
Jonathan M. Green: Washington University School of Medicine
Kelly A. Brett: Washington University School of Medicine
Kenneth M. Murphy: Washington University School of Medicine, and Howard Hughes Medical Institute
John P. Atkinson: Washington University School of Medicine

Nature, 2003, vol. 421, issue 6921, 388-392

Abstract: Abstract The immune system must distinguish not only between self and non-self, but also between innocuous and pathological foreign antigens to prevent unnecessary or self-destructive immune responses. Unresponsiveness to harmless antigens is established through central and peripheral processes1. Whereas clonal deletion and anergy are mechanisms of peripheral tolerance2,3, active suppression by T-regulatory 1 (Tr1) cells has emerged as an essential factor in the control of autoreactive cells4. Tr1 cells are CD4+ T lymphocytes that are defined by their production of interleukin 10 (IL-10)5 and suppression of T-helper cells6; however, the physiological conditions underlying Tr1 differentiation are unknown. Here we show that co-engagement of CD3 and the complement regulator CD46 in the presence of IL-2 induces a Tr1-specific cytokine phenotype in human CD4+ T cells. These CD3/CD46-stimulated IL-10-producing CD4+ cells proliferate strongly, suppress activation of bystander T cells and acquire a memory phenotype. Our findings identify an endogenous receptor-mediated event that drives Tr1 differentiation and suggest that the complement system has a previously unappreciated role in T-cell-mediated immunity and tolerance.

Date: 2003
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/nature01315 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:421:y:2003:i:6921:d:10.1038_nature01315

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature01315

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().