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Immunol Lett. 2014 Mar-Apr;158(1-2):134-42. doi: 10.1016/j.imlet.2013.12.020. Epub 2014 Jan 8.

CD28 ligation in the absence of TCR stimulation up-regulates IL-17A and pro-inflammatory cytokines in relapsing-remitting multiple sclerosis T lymphocytes.

Author information

1
Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Biology and Biotechnology Charles Darwin, Sapienza University, Via dei sardi 70, 00185 Rome, Italy.
2
Neuroimmunology Unit, IRCCS Santa Lucia Foundation, 00179 Rome, Italy.
3
Neurology and Center for Experimental Neurological Therapies (CENTERS), S. Andrea Hospital, Sapienza University of Rome, 00189 Rome, Italy.
4
Department of Neurosciences, S. Camillo/Forlanini Hospital, 00151 Rome, Italy.
5
Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Biology and Biotechnology Charles Darwin, Sapienza University, Via dei sardi 70, 00185 Rome, Italy. Electronic address: loretta.tuosto@uniroma1.it.

Abstract

CD28 is a crucial costimulatory receptor necessary full T cell activation. The role of CD28 in multiple sclerosis (MS) has been evaluated as the source of costimulatory signals integrating those delivered by TCR. However, CD28 is also able to act as a unique signaling receptor and to deliver TCR-independent autonomous signals, which regulate the expression and production of pro-inflammatory cytokines and chemokines. By comparing the cytokine/chemokine profiles of CD4(+) T cells from relapsing-remitting multiple sclerosis (RRMS) patients and healthy donors (HD), we found that CD28 engagement without TCR strongly up-regulates IL-8 and IL-6 expression in RRMS compared to HD. More interestingly, in RRMS but not in HD, CD28 stimulation selectively induces the expression of IL-17A by cooperating with IL-6-mediated signals. By using specific inhibitory drugs, we also identify the phosphatidylinositol 3 kinase (PI3K) as the critical regulator of CD28 proinflammatory functions in MS.

KEYWORDS:

Costimulation: Multiple sclerosis; Inflammation: Th17 cells; PI3K

PMID:
24412596
DOI:
10.1016/j.imlet.2013.12.020
[Indexed for MEDLINE]

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