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.
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.
Khademi
Mohsen
M
Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden. mohsen.khademi@cmm.ki.se
Illés
Zsolt
Z
Gielen
Alexander W
AW
Marta
Monica
M
Takazawa
Naruhiko
N
Baecher-Allan
Claire
C
Brundin
Lou
L
Hannerz
Jan
J
Martin
Claes
C
Harris
Robert A
RA
Hafler
David A
DA
Kuchroo
Vijay K
VK
Olsson
Tomas
T
Piehl
Fredrik
F
Wallström
Erik
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D002460:Cell Line; D016764:Cell Polarity; D002555:Cerebrospinal Fluid / Q000166:cytology / Q000378:metabolism; D016207:Cytokines / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D000072596:Hepatitis A Virus Cellular Receptor 1; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D011991:Receptors, Virus / Q000235:genetics*; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*
D016207:Cytokines; C491143:HAVCR1 protein, human; C448908:HAVCR2 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D000072597:Hepatitis A Virus Cellular Receptor 2; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D011991:Receptors, Virus