Involvement of ICOS-B7RP-1 costimulatory pathway in the regulation of immune responses to Leishmania major and Nippostrongylus brasiliensis infections.
The ICOS-B7RP-1-mediated T cell costimulatory pathway has been implicated crucial for T cell activation and differentiation. In this study, we investigated the role of this costimulation in the regulation of immune responses to parasitic infections by using blocking antibody against B7RP-1 as well as ICOS-deficient mice. The administration of anti-B7RP-1 monoclonal antibody (mAb) significantly suppressed the footpad swelling in susceptible BALB/c mice upon Leishmania major infection. The observation was consistent not only with the significant suppression of IL-4, IL-5 and IL-10 secretion from lymph node cells, which were derived from L. major-infected mice, but also with the significant reduction of total serum IgE and IgG(1) in anti-B7RP-1 mAb-treated BALB/c mice. Infection of ICOS-deficient mice with L. major also suggested the impaired Th2 immune responses in the absence of this costimulation. The immunological function of ICOS-B7RP-1 costimulatory pathway in infection was further confirmed by infecting anti-B7RP-1 mAb-treated wild type or ICOS-deficient mice with Nippostrongylus brasiliensis. The characteristic elevation of total serum IgE and eosinophilia upon N. brasiliensis infection was suppressed by blocking this costimulation. Moreover, the protection to N. brasiliensis adult worms was suppressed in anti-B7RP-1 mAb-treated wild type or ICOS-deficient mice. These results suggest the crucial role of this costimulatory pathway in the regulation of Th2-biased T cell differentiation and in host immune responses against L. major and N. brasiliensis infections.
Miyahira
Yasushi
Y
Department of Molecular and Cellular Parasitology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, 113-8421, Tokyo, Japan.
Akiba
Hisaya
H
Ogawa
Shu-Hei
SH
Ishi
Tomohiro
T
Watanabe
Shiho
S
Kobayashi
Seiki
S
Takeuchi
Tsutomu
T
Aoki
Takashi
T
Tezuka
Katsunari
K
Abe
Ryo
R
Okumura
Ko
K
Yagita
Hideo
H
Watanabe
Naohiro
N
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000502:physiology*; D018122:B7-1 Antigen / Q000276:immunology / Q000502:physiology*; D007107:Immune System / Q000276:immunology / Q000502:physiology*; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D018320:Leishmania major / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009559:Nippostrongylus / Q000276:immunology; D017206:Strongylida Infections / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology / Q000502:physiology
D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; C556694:Icos protein, mouse; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein