Myelin-reactive T-lymphocyte

Myelin-reactive T-lymphocytes are the primary drivers of neuroinflammation in relapsing-remitting multiple sclerosis (RRMS). These autoaggressive cells, predominantly of the Th1 and Th17 phenotypes, are primed in the periphery against myelin antigens such as myelin basic protein (MBP), proteolipid protein (PLP), and myelin oligodendrocyte glycoprotein (MOG) [1]. Upon activation, they express high levels of the alpha-4 beta-1 integrin (VLA-4), allowing them to adhere to the vascular endothelium and extravasate across the blood-brain barrier into the central nervous system (CNS) [2]. Within the CNS, these T-cells are reactivated by local antigen-presenting cells, leading to the secretion of pro-inflammatory cytokines like IFN-gamma and IL-17, which promote demyelination, oligodendrocyte death, and axonal degeneration [3]. Pharmacological targeting of these cells includes depletion strategies using monoclonal antibodies like Alemtuzumab (anti-CD52), sequestration in lymph nodes via S1P receptor modulators like Fingolimod, and trafficking blockade using Natalizumab [4]. While these therapies significantly reduce relapse rates, they carry risks of serious adverse effects, such as progressive multifocal leukoencephalopathy (PML) and secondary autoimmune disorders [5]. Future directions focus on antigen-specific therapies that aim to induce tolerance in these specific T-cell subsets without compromising the broader immune system [6]. References: [1] Kaskow & Baecher-Allan (2018) Cold Spring Harb Perspect Med; [2] Goverman (2009) Nat Rev Immunol; [3] Dendrou et al. (2015) Nat Rev Immunol; [4] Hauser & Cree (2020) Am J Med; [5] Bloomgren et al. (2012) N Engl J Med; [6] Lutterotti & Martin (2014) Expert Opin Investig Drugs.

Other names

Disease-specific autoaggressive T-cellsMyelin-specific T-cellsEncephalitogenic T-cellsAutoreactive T-lymphocytesMyelin-reactive T-cells

Therapeutic strategies include the systemic depletion of lymphocyte populations, the inhibition of lymphocyte egress from secondary lymphoid organs through S1P receptor modulation, and the blockade of leukocyte migration across the blood-brain barrier by inhibiting alpha-4 integrins.