Back to Search
Start Over
Engagement of distinct epitopes on CD43 induces different co-stimulatory pathways in human T cells
- Source :
- Immunology
- Publication Year :
- 2016
-
Abstract
- Summary Co‐receptors, being either co‐stimulatory or co‐inhibitory, play a pivotal role in T‐cell immunity. Several studies have indicated that CD43, one of the abundant T‐cell surface glycoproteins, acts not only as a potent co‐receptor but also as a negative regulator for T‐cell activation. Here we demonstrate that co‐stimulation of human peripheral blood (PB) T cells through two distinct CD43 epitopes recognized by monoclonal antibodies (mAb) CD43‐6E5 (T6E5‐act) and CD43‐10G7 (T10G7‐act) potently induced T‐cell proliferation. However, T‐cell co‐stimulation through two CD43 epitopes differentially regulated activation of nuclear factor of activated T cells (NFAT) and nuclear factor‐κB (NF‐κB) transcription factors, T‐cell cytokine production and effector function. T6E5‐act produced high levels of interleukin‐22 (IL‐22) and interferon‐γ (IFN‐γ) similar to T cells activated via CD28 (TCD 28‐act), whereas T10G7‐act produced low levels of inflammatory cytokines but higher levels of regulatory cytokines transforming growth factor‐β (TGF‐β) and interleukin‐35 (IL‐35). Compared with T6E5‐act or to TCD 28‐act, T10G7‐act performed poorly in response to re‐stimulation and further acquired a T‐cell suppressive function. T10G7‐act did not directly inhibit proliferation of responder T cells, but formed stable heterotypic clusters with dendritic cells (DC) via CD2 to constrain activation of responder T cells. Together, our data demonstrate that CD43 is a unique and polarizing regulator of T‐cell function.
- Subjects :
- Leukosialin
NFATC Transcription Factors
NF-kappa B
Receptors, Antigen, T-Cell
Epitopes, T-Lymphocyte
Cell Differentiation
Dendritic Cells
Receptor Cross-Talk
Original Articles
T-Lymphocytes, Regulatory
co‐stimulation
heterotypic cell adhesion
suppressor T cells
CD28 Antigens
Costimulatory and Inhibitory T-Cell Receptors
T-Lymphocyte Subsets
Immune Tolerance
Cytokines
Humans
CD43
Original Article
T‐cell polarization
Cells, Cultured
Signal Transduction
Subjects
Details
- ISSN :
- 13652567
- Volume :
- 149
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Immunology
- Accession number :
- edsair.pmid..........6008a10c7b269aec5430486de1efd62c