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, John P. Atkinson

Research output: Contribution to journalArticlepeer-review

474 Scopus citations

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 processes. Whereas clonal deletion and anergy are mechanisms of peripheral tolerance, active suppression by T-regulatory 1 (Tr1) cells has emerged as an essential factor in the control of autoreactive cells. Tr1 cells are CD4+ T lymphocytes that are defined by their production of interleukin 10 (IL-10) and suppression of T-helper cells; 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.

Original languageEnglish
Pages (from-to)388-392
Number of pages5
JournalNature
Volume421
Issue number6921
DOIs
StatePublished - Jan 23 2003

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