Abstract
It is now clear that functionally specialized regulatory T (Treg) cells exist as part of the normal immune repertoire, preventing the development of pathogenic responses to both self- and intestinal antigens. Here, we report that the Treg cells that control intestinal inflammation express the same phenotype (CD25+CD45RBlowCD4+) as those that control autoimmunity. Previous studies have failed to identify how CD25+ Treg cells function in vivo. Our studies reveal that the immune-suppressive function of these cells in vivo is dependent on signaling via the negative regulator of T cell activation cytotoxic T lymphocyte–associated antigen 4 (CTLA-4), as well as secretion of the immune-suppressive cytokine transforming growth factor β. Strikingly, constitutive expression of CTLA-4 among CD4+ cells was restricted primarily to Treg cells, suggesting that CTLA-4 expression by these cells is involved in their immune-suppressive function. These findings raise the possibility that Treg cell function contributes to the immune suppression characteristic of CTLA-4 signaling. Identification of costimulatory molecules involved in the function of Treg cells may facilitate further characterization of these cells and development of new therapeutic strategies for the treatment of inflammatory diseases.
Keywords
IL-2 receptorCytotoxic T cellImmune systemBiologyImmunologyAntigenRegulatory T cellCTLA-4InflammationAntigen-presenting cellT cellCell biologyInterleukin 21In vitro
MeSH Terms
AbataceptAnimalsAntigensCDAntigensDifferentiationCD4-Positive T-LymphocytesCTLA-4 AntigenColitisImmunoconjugatesLeukocyte Common AntigensMiceMiceInbred BALB CMiceInbred C57BLReceptorsInterleukin-2T-LymphocytesRegulatoryTransforming Growth Factor beta
Affiliated Institutions
Related Publications
Immunologic Self-Tolerance Maintained by Cd25+Cd4+Regulatory T Cells Constitutively Expressing Cytotoxic T Lymphocyte–Associated Antigen 4
This report shows that cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) plays a key role in T cell–mediated dominant immunologic self-tolerance. In vivo blockade of CTLA-4 f...
Unique Chemotactic Response Profile and Specific Expression of Chemokine Receptors Ccr4 and Ccr8 by Cd4+Cd25+ Regulatory T Cells
Chemokines dictate regional trafficking of functionally distinct T cell subsets. In rodents and humans, a unique subset of CD4+CD25+ cytotoxic T lymphocyte antigen (CTLA)-4+ reg...
Phenotype, Localization, and Mechanism of Suppression of CD4<b>+</b>CD25<b>+</b> Human Thymocytes
Phenotypic markers, localization, functional activities, and mechanisms of action in vitro of CD4+CD25+ T cells, purified from postnatal human thymuses, were investigated. These...
Conversion of Peripheral CD4+CD25− Naive T Cells to CD4+CD25+ Regulatory T Cells by TGF-β Induction of Transcription Factor <i>Foxp3 </i>
CD4+CD25+ regulatory T cells (Treg) are instrumental in the maintenance of immunological tolerance. One critical question is whether Treg can only be generated in the thymus or ...
Expression of the integrin α<sub>E</sub>β<sub>7</sub>identifies unique subsets of CD25<sup>+</sup>as well as CD25<sup>−</sup>regulatory T cells
Regulatory CD25 + CD4 + T cells are considered as important players in T cell homeostasis and self-tolerance. Here we report that the integrin α E β 7 , which recognizes epithel...
Publication Info
- Year
- 2000
- Type
- article
- Volume
- 192
- Issue
- 2
- Pages
- 295-302
- Citations
- 2165
- Access
- Closed
External Links
Social Impact
Altmetric
PlumX Metrics
Social media, news, blog, policy document mentions
Citation Metrics
2165
OpenAlex
150
Influential
1718
CrossRef
Cite This
Simon Read,
Vivianne Malmström,
Fiona Powrie
(2000).
Cytotoxic T Lymphocyte–Associated Antigen 4 Plays an Essential Role in the Function of Cd25+Cd4+ Regulatory Cells That Control Intestinal Inflammation.
The Journal of Experimental Medicine
, 192
(2)
, 295-302.
https://doi.org/10.1084/jem.192.2.295
Identifiers
- DOI
- 10.1084/jem.192.2.295
- PMID
- 10899916
- PMCID
- PMC2193261