T Cell Ig- and Mucin-Domain-Containing Molecule-3(TIM-3)and TIM-1 Molecules Are Differentially Expressed on Human Thl and Th2 Cells and in Cerebrospinal Fluid-Derived Mononuclear Cells in Multiple Sclerosis

摘要

T cell Ig- and mucin-domain-containing molecules(TIMs)comprise a recently described family of molecules expressed on T cells.TIM-3 has been shown to be expressed on murine Thl cell clones and has been implicated in the pathogenesis of Thl-driven experimental autoimmune encephalomyelitis.In contrast,association of TIM-1 polymorphisms to Th2-related airway hyperre-activity has been suggested in mice.The TIM molecules have not been investigated in human Thl- or Th2-mediated diseases.Using real-time(TaqMan)RT-PCR,we show that human Thl lines expressed higher TIM-3 mRNA levels,while Th2 lines demonstrated a higher expression of TIM-1.Analysis of cerebrospinal fluid mononuclear cells obtained from patients with multiple sclerosis revealed significantly higher mRNA expression of TIM-1 compared with controls.Moreover,higher TIM-1 expression was associated with clinical remissions and low expression of IFN-y mRNA in cerebrospinal fluid mononuclear cells.In contrast,expression of TIM-3 correlated well with high expression of IFN-gamma and TNF-alpha.These data imply the differential expression of human TIM molecules by Thl and Th2 cells and may suggest their differential involvement in different phases of a human autoimmune disease.