Effects of interferon- on co-signaling molecules: upregulation of CD40, CD86 and PD-L2 on monocytes in relation to clinical response to interferon- treatment in patients with multiple sclerosis

¹ Department of Neurology, Medical School Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
² Department of Neurology, Klinikum rechts der isar, Technische Universität Munich, Germany

^* To whom correspondence should be addressed.

	Abstract

Interferon-beta (IFN-) reduces disease activity in a subgroup of patients with relapsing remitting multiple sclerosis (MS). The mechanism of action as well as the pathophysiological basis of responsiveness to IFN- is not well understood. Since T-cell activation plays an important part in the pathophysiology of MS, we here investigated the effect of IFN- on the expression of co-signaling pathways (CD28–CD80/CD86, CD154–CD40, ICOS–ICOSL, PD-1–PD-L1/2) in MS patients and correlated the results with the clinical response to IFN- in individual patients. Expression of co-signaling molecules was measured by flow cytometry in vitro on peripheral blood mononuclear cells after incubation with IFN-, and in vivo in whole blood samples of 32 untreated and 24 IFN- treated MS patients, including 13 patients longitudinal. IFN- treatment induced upregulation of CD40, CD80, CD86, PD-L1 and PD-L2 on monocytes as well as PD-L1 on CD4¹-T-cells in vitro and in vivo. IFN- treated MS patients were grouped into responders and non-responders on the basis of Kurtzkés EDSS (expanded disability status scale) progression and relapse rate. Upregulation of CD40, CD86 and PD-L2 on monocytes was associated with treatment response to IFN- (P < 0.001, P = 0.028 and P = 0.028, respectively).

Our results show that IFN- upregulates co-stimulatory as well as co-inhibitory molecules in vitro and in vivo implicating that modulation of the balance between positive and negative co-stimulatory signals might be an important part of the mechanism of action of IFN- in MS. Upregulation of the expression of CD40, CD86 and PD-L2 may be useful as a predictive marker for clinical response to IFN- treatment at early timepoints during IFN- therapy.

Key Words: B7 family; co-stimulatory molecules; interferon-beta; multiple sclerosis; PD-L1; PD-L2

First published on October 17, 2007, doi:10.1177/1352458507081342

Multiple Sclerosis 2008;14:166.

A more recent version of this article appeared on March 1, 2008


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