T Cell Ig- and Mucin-Domain-Containing Molecule-3 (TIM-3) and TIM-1 Molecules Are Differentially Expressed on Human Th1 and Th2 Cells and in Cerebrospinal Fluid-Derived Mononuclear Cells in Multiple Sclerosis

• Published in: The Journal of immunology (1950) Vol. 172; no. 11; pp. 7169 - 7176
• Main Authors: Khademi, Mohsen, Illes, Zsolt, Gielen, Alexander W, Marta, Monica, Takazawa, Naruhiko, Baecher-Allan, Claire, Brundin, Lou, Hannerz, Jan, Martin, Claes, Harris, Robert A, Hafler, David A, Kuchroo, Vijay K, Olsson, Tomas, Piehl, Fredrik, Wallstrom, Erik
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01-06-2004
• Subjects: Adolescent; Adult; Aged; Cell Line; Cell Polarity; Cerebrospinal Fluid - cytology; Cerebrospinal Fluid - metabolism; Cytokines - genetics; Female; Gene Expression Regulation; Hepatitis A Virus Cellular Receptor 1; Hepatitis A Virus Cellular Receptor 2; Humans; Male; Medicin och hälsovetenskap; Membrane Glycoproteins - genetics; Membrane Proteins - genetics; Middle Aged; Multiple Sclerosis - cerebrospinal fluid; Multiple Sclerosis - immunology; Receptors, Virus - genetics; RNA, Messenger - analysis; Th1 Cells - metabolism; Th2 Cells - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.172.11.7169

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 Th1 cell clones and has been implicated in the pathogenesis of Th1-driven experimental autoimmune encephalomyelitis. In contrast, association of TIM-1 polymorphisms to Th2-related airway hyperreactivity has been suggested in mice. The TIM molecules have not been investigated in human Th1- or Th2-mediated diseases. Using real-time (TaqMan) RT-PCR, we show that human Th1 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-gamma 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 Th1 and Th2 cells and may suggest their differential involvement in different phases of a human autoimmune disease.