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T regulatory cell chemokine production mediates pathogenic T cell attraction and suppression
- Source :
- Journal of Clinical Investigation. 126:1039-1051
- Publication Year :
- 2016
- Publisher :
- American Society for Clinical Investigation, 2016.
-
Abstract
- T regulatory cells (Tregs) control immune homeostasis by preventing inappropriate responses to self and nonharmful foreign antigens. Tregs use multiple mechanisms to control immune responses, all of which require these cells to be near their targets of suppression; however, it is not known how Treg-to-target proximity is controlled. Here, we found that Tregs attract CD4+ and CD8+ T cells by producing chemokines. Specifically, Tregs produced both CCL3 and CCL4 in response to stimulation, and production of these chemokines was critical for migration of target T cells, as Tregs from Ccl3–/– mice, which are also deficient for CCL4 production, did not promote migration. Moreover, CCR5 expression by target T cells was required for migration of these cells to supernatants conditioned by Tregs. Tregs deficient for expression of CCL3 and CCL4 were impaired in their ability to suppress experimental autoimmune encephalomyelitis or islet allograft rejection in murine models. Moreover, Tregs from subjects with established type 1 diabetes were impaired in their ability to produce CCL3 and CCL4. Together, these results demonstrate a previously unappreciated facet of Treg function and suggest that chemokine secretion by Tregs is a fundamental aspect of their therapeutic effect in autoimmunity and transplantation.
- Subjects :
- Male
0301 basic medicine
Adoptive cell transfer
Chemokine
Encephalomyelitis, Autoimmune, Experimental
Adolescent
Receptors, CCR5
T cell
Mice, Transgenic
chemical and pharmacologic phenomena
Biology
T-Lymphocytes, Regulatory
Diabetes Mellitus, Experimental
03 medical and health sciences
Immune system
Antigen
parasitic diseases
medicine
Animals
Humans
Chemokine CCL4
Child
Cells, Cultured
Cell Proliferation
Chemokine CCL3
Mice, Inbred BALB C
Infant
hemic and immune systems
General Medicine
Adoptive Transfer
Mice, Inbred C57BL
Transplantation
Chemotaxis, Leukocyte
Diabetes Mellitus, Type 1
030104 developmental biology
medicine.anatomical_structure
Child, Preschool
Immunology
Chemokine secretion
biology.protein
Female
CD8
Research Article
Subjects
Details
- ISSN :
- 15588238 and 00219738
- Volume :
- 126
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Investigation
- Accession number :
- edsair.doi.dedup.....d8fed5e77de53b00eeb85648708615fb