TIM-1 induces T cell activation and inhibits the development of peripheral tolerance.
We have examined the function of TIM-1, encoded by a gene identified as an 'atopy susceptibility gene' (Havcr1*), and demonstrate here that TIM-1 is a molecule that costimulates T cell activation. TIM-1 was expressed on CD4(+) T cells after activation and its expression was sustained preferentially in T helper type 2 (T(H)2) but not T(H)1 cells. In vitro stimulation of CD4(+) T cells with a TIM-1-specific monoclonal antibody and T cell receptor ligation enhanced T cell proliferation; in T(H)2 cells, such costimulation greatly enhanced synthesis of interleukin 4 but not interferon-gamma. In vivo, the use of antibody to TIM-1 plus antigen substantially increased production of both interleukin 4 and interferon-gamma in unpolarized T cells, prevented the development of respiratory tolerance, and increased pulmonary inflammation. Our studies suggest that immunotherapies that regulate TIM-1 function may downmodulate allergic inflammatory diseases.
Umetsu
Sarah E
SE
Department of Pediatrics, Stanford University, Stanford, California 94305, USA.
Lee
Wan-Ling
WL
McIntire
Jennifer J
JJ
Downey
Laura
L
Sanjanwala
Bharati
B
Akbari
Omid
O
Berry
Gerald J
GJ
Nagumo
Haruo
H
Freeman
Gordon J
GJ
Umetsu
Dale T
DT
DeKruyff
Rosemarie H
RH
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000473:pathology / Q000628:therapy; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D000072596:Hepatitis A Virus Cellular Receptor 1; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology*; D007167:Immunotherapy; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*
D000906:Antibodies; C442240:Havcr1 protein, mouse; D000072596:Hepatitis A Virus Cellular Receptor 1; D008565:Membrane Proteins