Journal article
TCR stimulation with modified anti-CD3 mAb expands CD8+ T cell population and induces CD8+CD25+ Tregs
The Journal of clinical investigation, Vol.115(10), pp.2904-2913
10/01/2005
DOI: 10.1172/JCI23961
PMCID: PMC1201661
PMID: 16167085
Abstract
Modified anti-CD3 mAbs are emerging as a possible means of inducing immunologic tolerance in settings including transplantation and autoimmunity such as in type 1 diabetes. In a trial of a modified anti-CD3 mAb [hOKT3γ1(Ala-Ala)] in patients with type 1 diabetes, we identified clinical responders by an increase in the number of peripheral blood CD8
+
cells following treatment with the mAb. Here we show that the anti-CD3 mAb caused activation of CD8
+
T cells that was similar in vitro and in vivo and induced regulatory CD8
+
CD25
+
T cells. These cells inhibited the responses of CD4
+
cells to the mAb itself and to antigen. The regulatory CD8
+
CD25
+
cells were CTLA4
+
and Foxp3
+
and required contact for inhibition. Foxp3 was also induced on CD8
+
T cells in patients during mAb treatment, which suggests a potential mechanism of the anti-CD3 mAb immune modulatory effects involving induction of a subset of regulatory CD8
+
T cells.
Details
- Title: Subtitle
- TCR stimulation with modified anti-CD3 mAb expands CD8+ T cell population and induces CD8+CD25+ Tregs
- Creators
- Brygida Bisikirska - Department of Medicine andJohn Colgan - Department of Medicine andJeremy Luban - Department of Medicine andJeffrey A Bluestone - Department of Medicine andKevan C Herold - Department of Medicine and
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.115(10), pp.2904-2913
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/JCI23961
- PMID
- 16167085
- PMCID
- PMC1201661
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 10/01/2005
- Academic Unit
- Anatomy and Cell Biology; Immunology; Internal Medicine
- Record Identifier
- 9984025667602771
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