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Modulation of CD4 T cell function via CD6-targeting
- Source :
- EBioMedicine
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- In recent years molecules involved on the immune synapse became successful targets for therapeutic immune modulation. CD6 has been extensively studied, yet, results regarding CD6 biology have been controversial, in spite of the ubiquitous presence of this molecule on virtually all CD4 T cells. We investigated the outcome of murine and human antibodies targeting CD6 domain 1. We found that CD6-targeting had a major impact on the functional specialization of CD4 cells, both human and murine. Differentiation of CD4 T cells towards a Foxp3+ Treg fate was prevented with increasing doses of anti-CD6, while Th1 polarization was favoured. No impact was observed on Th2 or Th17 specialization. These in vitro results provided an explanation for the dose-dependent outcome of in vivo anti-CD6 administration where the anti-inflammatory action is lost at the highest doses. Our data show that therapeutic targeting of the immune synapse may lead to paradoxical dose-dependent effects due to modification of T cell fate. Funded by UID/BIM/50005/2019, project funded by Fundação para a Ciência e a Tecnologia (FCT) / Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) throught Fundos do Orçamento do Estado, pela Fundação para a Ciência e a Tecnologia (FCT) ( PTDC/DTP-FTO/3080/2014 ); and by the project SRecognite Infect - ERA/0003/2015 using national funds through FCT . Funders did not have a role in study design, data collection, analysis, and interpretation, or in the writing of the manuscript.
- Subjects :
- Antigens, Differentiation, T-Lymphocyte
CD4-Positive T-Lymphocytes
Fetal Proteins
CD4-Positive T-Lymphocytes / metabolism
0301 basic medicine
Research paper
Lymphocyte Activation
Immunological synapse
Mice
0302 clinical medicine
T-Lymphocyte Subsets
Cell Adhesion Molecules, Neuronal / metabolism
Antigens, Differentiation, T-Lymphocyte / metabolism
Cd4 t cell
EAE
FOXP3
Cell Differentiation
General Medicine
T-cell polarization
Cell biology
medicine.anatomical_structure
Foxp3
030220 oncology & carcinogenesis
Antibody
Cell Adhesion Molecules, Neuronal
T cell
CD4 T cells
Mice, Transgenic
Biology
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Antigens, CD
In vivo
CD4-Positive T-Lymphocytes / immunology
medicine
Animals
Humans
T-Lymphocyte Subsets / metabolism
Antigens, CD / metabolism
CD4-Positive T-Lymphocytes / cytology
CD6
Fetal Proteins / metabolism
In vitro
030104 developmental biology
biology.protein
Treg cells
Biomarkers
Function (biology)
T-Lymphocyte Subsets / immunology
Subjects
Details
- ISSN :
- 23523964
- Volume :
- 47
- Database :
- OpenAIRE
- Journal :
- EBioMedicine
- Accession number :
- edsair.doi.dedup.....000c3982119e1bc616c460837851466b