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Inhibition of T cell proliferation by cholera toxin involves the modulation of costimulatory molecules CTLA-4 and CD28

TitoloInhibition of T cell proliferation by cholera toxin involves the modulation of costimulatory molecules CTLA-4 and CD28
Tipo di pubblicazioneArticolo su Rivista peer-reviewed
Anno di Pubblicazione2008
AutoriVendetti, S., Riccomi A., Sacchi A., Sciaraffia E., Gatta L., Pioli Claudio, and De Magistris M.T.
RivistaImmunology Letters
Volume115
Paginazione59-69
ISSN01652478
Parole chiaveantigen expression, antigen function, antigenic modulation, Antigens, article, CD, CD28, CD28 antigen, CD3 antibody, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, cell activation, Cell cycle, cell cycle arrest, cell cycle G0 phase, cell cycle G1 phase, cell function, cell membrane, cell proliferation, cholera toxin, controlled study, cytotoxic T lymphocyte antigen 4, Differentiation, DNA, DNA content, DNA determination, human, human cell, Humans, Leukocytes, lymphocyte activation, messenger RNA, molecule, Monoclonal antibody, Mononuclear, priority journal, protein expression, T lymphocyte, T lymphocyte activation, T lymphocyte subpopulation
Abstract

Cholera toxin (CT) is known to inhibit the proliferation of murine and human T lymphocytes. In this study we have analysed the mechanisms underlying the inhibitory effect of CT on subpopulations of human CD4+ and CD8+ T lymphocytes. We show that CT dramatically prevents the activation of resting T lymphocytes, whereas it has a minor effect on cells that have been previously activated. Analysis of DNA content of the CT-treated T cells showed an arrest in the G0/G1 phase and this correlated with high expression of the cyclin-dependent kinase inhibitor p27kip. Moreover, we show that CT up-regulates the expression of the inhibitory molecule CTLA-4 in naïve, effector and memory resting CD4+ T cells and in resting CD8+ T lymphocytes. The regulation of CTLA-4 expression by CT is at the transcriptional level. Indeed, in cells treated with CT we observed an increase of two mRNA variants coding for the membrane and the soluble CTLA-4 molecules. In parallel with the up-regulation of the inhibitory CTLA-4, CT down-modulates the costimulatory molecule CD28 on CD4+ and CD8+ resting T cells. The increased expression of CTLA-4 played a role in controlling T cell activation and function as blocking anti-CTLA-4 F(ab′)2 mAbs partially inhibited anti-CD3 mAbs induced proliferation. These findings show that the inhibition of T cell proliferation by CT affects early stages of the T cell activation and involves the modulation of costimulatory molecules CTLA-4 and CD28 on resting T cells. © 2007 Elsevier B.V. All rights reserved.

Note

cited By 4

URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-37349021450&doi=10.1016%2fj.imlet.2007.10.003&partnerID=40&md5=36dc92683c1147a9534289f03dbc59a2
DOI10.1016/j.imlet.2007.10.003
Citation KeyVendetti200859