Interferon-ß Treatment In Multiple Sclerosis Decreases The Number Of Circulating T-Cells Producing Interferon- And InterLeukin-4
Furlan R, Bergami A, Lang R, Brambilla E, Franciotta D, Martinelli V, Comi G, Panina P, Martino G
J NeuroImmunol 2000 Nov 1;111(1-2):86-92
San Raffaele Scientific Institute, NeuroImmunology Unit-DIBIT, Dept . of NeuroScience, Via Olgettina 58, 20132, Milan, Italy
Systemic administration of Interferon-beta (IFN-ß) has been recently approved for the treatment of Relapsing/Remitting Multiple Sclerosis (RRMS).
The Immunological mechanism by which IFN-ß ameliorates MS is still partially unknown.
We measured the number of blood circulating CD4+, CD4-, CD8+, and CD8- T-Cells secreting IFN-.
And IL-4 in 26 RRMS patients followed for up to 9 months of an alternate day s.c. treatment with 8x16 IU of IFN-ß-1b.
Compared to pre-treatment values, a significant (P<0.05) reduction of CD4+, CD4-, CD8+ and CD8- Cells producing IFN-.
And of CD4+ and CD4- Cells producing IL-4 was observed in MS patients.
The IFN-ß-associated effect was evident soon after the beginning of the treatment and persisted for the entire follow-up period.
We did not observe any effect of IFN-ß treatment on the percentage of IL-4-producing CD8+ and CD8- Cells nor in that of Natural Killer (NK) Cells producing IFN-.
Our results show that IFN-ß treatment in MS patients induces a profound and persistent down-regulation of the number of circulating T-Cells secreting IFN-.
And IL-4 thus suggesting a broader rather than a specific ImmunoModulatory effect of IFN-ß in MS.
VLA-4/CD49d Downregulated On Primed T-Lymphocytes During Interferon-ß Therapy In Multiple Sclerosis
Muraro PA, Leist T, Bielekova B, McFarland HF
J NeuroImmunol 2000 Nov 1;111(1-2):186-194
National Institutes of Health, National Institute of Neurological Disorders and Stroke, NeuroImmunology Branch, 10 Center Drive MSC1400, 20892-1400, Bethesda, MD, USA
Effects on Adhesion Molecules of Immune Cells might contribute to the mode of action of Interferon-beta (IFN-ß) in Multiple Sclerosis (MS).
We have serially monitored the cell surface expression of Integrins CD49d (VLA-4) and CD11a (LFA-1) on fresh T-Lymphocyte subpopulations from 5 MS patients monthly for 2 months prior to treatment and for 3 months on treatment with IFN-ß-1b.
In parallel, we assessed inflammatory disease activity by monthly contrast-enhanced Magnetic Resonance Imaging (MRI).
IFN-ß treatment specifically downregulated CD49d expression on CD8+ and CD4+/CD45RO+ 'memory' T-Lymphocytes.
And differentially modulated the proportion of CD4+, CD8+ and CD27+ T-Cells.
These effects may play an important role in the reduction of Central Nervous System cell trafficking and inflammation in MS.
CD4+CD45RO+) CD49d (high) Cells Are Involved In The Pathogenesis Of Relapsing/Remitting Multiple Sclerosis
Barrau MA, Montalban X, Saez-Torres I, Brieva L, Barbera N, Martinez-Caceres EM
J NeuroImmunol 2000 Nov 1;111(1-2):215-223
Unitat de NeuroImmunologia Clinica, Servei de Neurologia, Hospital General Universitari Vall d'Hebron, Ps Vall d'Hebron 119-129, 08035, Barcelona, Spain
In the animal model of Multiple Sclerosis, Experimental AutoImmune EncephaloMyelitis, Encephalitogenic T-Cells differ from the non-Encephalitogenic ones in their expression of CD49d.
The disease-inducing CD49d (high) and not the CD49d (low) cells enter the Brain Parenchyma. In this context, we characterized CD4+ (CD45RO+ CD49d (high) cells in Relapsing/Remitting Multiple Sclerosis (RR-MS) patients.
These cells, showing characteristics of activated cells able to produce pro-inflammatory Cytokines, were found to be increased in peripheral blood during relapses and present in high numbers in CerebroSpinal Fluid.
These results suggest that the CD4+ CD45RO+ CD49d (high) subpopulation in RR-MS patients includes AutoReactive Cells and may be target for ImmunoTherapy.