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Engagement of distinct epitopes on CD43 induces different co-stimulatory pathways in human T cells.
- Source :
-
Immunology . Nov2016, Vol. 149 Issue 3, p280-296. 17p. - Publication Year :
- 2016
-
Abstract
- 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 ( TCD28-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 TCD28-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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00192805
- Volume :
- 149
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 118479460
- Full Text :
- https://doi.org/10.1111/imm.12642