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- Title
Activation of human CD4<sup>+</sup> cells with CD3 and CD46 induces a T-regulatory cell 1 phenotype.
- Authors
Kemper, Claudia; Chan, Andrew C.; Green, Jonathan M.; Brett, Kelly A.; Murphy, Kenneth M.; Atkinson, John P.
- 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.
- Subjects
T cells; CD antigens; IMMUNE response
- Publication
Nature, 2003, Vol 421, Issue 6921, p388
- ISSN
0028-0836
- Publication type
Article
- DOI
10.1038/nature01315