Antibodies to T-cell Ig and mucin domain-containing proteins (Tim)-1 and -3 suppress the induction and progression of murine allergic conjunctivitis.
The T cell Ig and mucin domain-containing proteins (Tim) regulate Th1- and Th2-mediated immune responses. We investigated the ability of Abs blocking Tim-1 or Tim-3 ligand-binding activity to prevent and treat murine experimental allergic conjunctivitis (EC), a Th2-mediated disease. Treatment with either Ab during the induction phase of EC in actively immunized wild-type mice suppressed EC and upregulated Th1 and Th2 immune responses. In contrast, both Abs exacerbated EC in actively immunized IFN-gamma-knockout mice. Thus, both anti-Tim Abs suppress the pathogenic immune responses generated in the induction phase by upregulating systemic IFN-gamma production. Treatment of actively immunized mice and passively immunized mice with either anti-Tim Ab just prior to RW challenge also suppressed EC. Thus, treatment with anti-Tim-1 or anti-Tim-3 Ab can suppress both the induction and progression of EC, which could indicate potential preventive and/or therapeutic approaches for allergic diseases such as allergic conjunctivitis.
Fukushima
Atsuki
A
Department of Ophthalmology and Visual Science, Kochi Medical School, Kohasu, Nankoku-city 783-8505, Japan. fukusima@med.kochi-u.ac.jp
Sumi
Tamaki
T
Fukuda
Ken
K
Kumagai
Naoki
N
Nishida
Teruo
T
Akiba
Hisaya
H
Okumura
Ko
K
Yagita
Hideo
H
Ueno
Hisayuki
H
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000627:therapeutic use*; D003233:Conjunctivitis, Allergic / Q000276:immunology* / Q000517:prevention & control; D000072597:Hepatitis A Virus Cellular Receptor 2; D007074:Immunoglobulin G / Q000276:immunology*; D016219:Immunotherapy, Adoptive / Q000379:methods; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation*
D000906:Antibodies; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D007074:Immunoglobulin G; D008565:Membrane Proteins; D011991:Receptors, Virus; C442242:Timd2 protein, mouse