Engagement of distinct epitopes on CD43 induces different co-stimulatory pathways in human T cells.
Immunology
; 149(3): 280-296, 2016 Nov.
Article
em En
| MEDLINE
| ID: mdl-27392084
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-ß (TGF-ß) 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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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Subpopulações de Linfócitos T
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Linfócitos T Reguladores
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Epitopos de Linfócito T
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Leucossialina
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article