Circulating immune cells in multiple sclerosis

Abstract

Summary Circulating T and B lymphocytes contribute to the pathogenesis of the neuroinflammatory autoimmune disease, multiple sclerosis (MS). Further progress in the development of MS treatments is dependent upon a greater understanding of the immunological disturbances that underlie the disease. Analyses of circulating immune cells by flow cytometry have revealed MS‐associated alterations in the composition and function of T and B cell subsets, including temporal changes associated with disease activity. Disturbances in circulating immune populations reflect those observed in the central nervous system and include skewing towards proinflammatory CD4+ and CD8+ T cells and B cells, greater proportions of follicular T helper cells and functional defects in the corresponding T and B regulatory subsets. Utilizing the analytical power of modern flow cytometers, researchers are now well positioned to monitor immunological changes associated with disease activity or intervention, describe immunological signatures with predictive value and identify targets for therapeutic drug development. This review discusses the contribution of various T and B lymphocyte subsets to MS pathogenesis, provides current and relevant phenotypical descriptions to assist in experimental design and highlights areas of future research.

Altered regulatory T‐cell fractions and Helios expression in clinically isolated syndrome: clues to the development of multiple sclerosis

“…In contrast to results of the current study, transitional B cells have been reported at lower frequency in CIS and relapsing–remitting MS by one group 27 but at similar frequency to HC by another 28 . Shifts within the B‐cell compartment reportedly occur in a temporal relationship with MS disease activity 5 . Thus an increase in circulating transitional B cells may indicate increased B‐cell release from the bone marrow in response to migration of mature B cells to sites of inflammation.…”

“…Functional impairment of Treg cells is commonly reported in MS studies; however, conventional analyses have failed to describe corresponding phenotypic characteristics 5 . In light of the work by Sakaguchi and colleagues, 11 it was our hypothesis that conventional definitions, such as those used in previous MS studies, obfuscate the functional heterogeneity of FoxP3 + Treg cells and that the CD45RA/FoxP3 fraction approach to analysis would yield more informative results.…”

“…GC in secondary lymphoid organ B‐cell follicles are the site of class switching, somatic hypermutation, differentiation into long‐lived memory or plasma cells and high‐affinity B‐cell selection 7 . Formation of GC and the continued GC reaction are dependent on help provided to B cells by C‐X‐C motif chemokine receptor 5 (CXCR5)‐expressing follicular T helper (Tfh) cells, 7 of which there are several subsets with varying degrees of helper capacity 5 . Inhibition of Tfh cells, GC B cells and subsequently the maintenance of normal GC responses is further dependent on follicular T regulatory (Tfr) cells 7 .…”

“…Beyond T‐–B‐cell interactions at the GC, impaired Treg function is associated with suboptimal suppression of autoreactive interferon (IFN)‐γ, interleukin (IL)‐17 and granulocyte‐macrophage colony‐stimulating factor‐producing CD4 + T cells, 9 , 10 that is, cells critical to blood–brain barrier degradation and attraction of peripheral immune cells to the central nervous system. However, despite numerous investigations the phenotype of functionally impaired Treg, in terms of surface or intracellular marker expression, is yet to be decisively demonstrated 5 . The same is largely true of B cells, where phenotypic descriptions of pathogenic and regulatory subsets remain incomplete 5 …”

RANKL/RANK/OPG Axis Is Deregulated in the Cerebrospinal Fluid of Multiple Sclerosis Patients at Clinical Onset

“…Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS) characterized by damage to the brain and spinal-cord white matter and thus causing significant neurologic impairment and disability [1,2]. In MS, cytokines and chemokines produced by activated myelin-reactive CD4+ helper T (Th) lymphocytes play a crucial role in triggering the disease onset, as well as in further development of the disease.…”