Regulatory T cells participate in 4-1BB-mediated suppression of experimental allergic conjunctivitis.
BACKGROUND
We showed previously that treatment with an agonistic anti-4-1BB Ab during the induction phase of murine experimental allergic conjunctivitis (EC) suppresses the development of this model disease. It was reported that 4-1BB promotes the expansion of regulatory T cells. Here we asked whether the suppression of EC by agonistic anti-4-1BB Ab treatment is mediated by regulatory T cells.


METHODS
Neonatal BALB/c mice were thymectomized and intraperitoneally injected with anti-CD25 Ab. At 6 weeks of age, these mice were immunized with ragweed (RW) in alum. As a control, immunocompetent BALB/c mice were immunized. Ten days later, the mice were challenged with RW in eye drops and 24 h later, the conjunctivas and spleens were harvested for histological and flow-cytometric analyses, respectively. The agonistic anti-4-1BB Ab or control normal rat IgG was injected intraperitoneally during the induction phase of EC.


RESULTS
With regard to immunocompetent mice, anti-4-1BB Ab treatment significantly suppressed the severity of EC as evaluated by conjunctival eosinophil numbers. In contrast, in thymectomized and anti-CD25 Ab-treated mice in which CD4+CD25+ regulatory T cells were efficiently depleted, anti-4-1BB Ab treatment did not affect the severity of EC.


CONCLUSIONS
These results indicate that CD4+CD25+ regulatory T cells play a critical role in the suppression of EC by anti-4-1BB Ab treatment.
Sumi
Tamaki
T
Department of Ophthalmology, Kochi Medical School, Kohasu Oko-cho, Nankoku City, Japan.
Ishida
Waka
W
Mittler
Robert S
RS
Yagita
Hideo
H
Taguchi
Osamu
O
Fukushima
Atsuki
A
D031164:Ambrosia / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D003228:Conjunctiva / Q000166:cytology / Q000187:drug effects; D003233:Conjunctivitis, Allergic / Q000276:immunology* / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004804:Eosinophils / Q000166:cytology; D007114:Immunization; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011058:Pollen / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D013934:Thymectomy; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9