Critical contribution of OX40 ligand to T helper cell type 2 differentiation in experimental leishmaniasis.
Infection of inbred mouse strains with Leishmania major is a well characterized model for analysis of T helper (Th)1 and Th2 cell development in vivo. In this study, to address the role of costimulatory molecules CD27, CD30, 4-1BB, and OX40, which belong to the tumor necrosis factor receptor superfamily, in the development of Th1 and Th2 cells in vivo, we administered monoclonal antibody (mAb) against their ligands, CD70, CD30 ligand (L), 4-1BBL, and OX40L, to mice infected with L. major. Whereas anti-CD70, anti-CD30L, and anti-4-1BBL mAb exhibited no effect in either susceptible BALB/c or resistant C57BL/6 mice, the administration of anti-OX40L mAb abrogated progressive disease in BALB/c mice. Flow cytometric analysis indicated that OX40 was expressed on CD4(+) T cells and OX40L was expressed on CD11c(+) dendritic cells in the popliteal lymph nodes of L. major-infected BALB/c mice. In vitro stimulation of these CD4(+) T cells showed that anti-OX40L mAb treatment resulted in substantially reduced production of Th2 cytokines. Moreover, this change in cytokine levels was associated with reduced levels of anti-L. major immunoglobulin (Ig)G1 and serum IgE. These results indicate that anti-OX40L mAb abrogated progressive leishmaniasis in BALB/c mice by suppressing the development of Th2 responses, substantiating a critical role of OX40-OX40L interaction in Th2 development in vivo.
Akiba
H
H
Department of Immunology, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
Miyahira
Y
Y
Atsuta
M
M
Takeda
K
K
Nohara
C
C
Futagawa
T
T
Matsuda
H
H
Aoki
T
T
Yagita
H
H
Okumura
K
K
D053330:4-1BB Ligand; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD; D053282:CD27 Ligand; D053285:CD30 Ligand; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D004195:Disease Models, Animal; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D016130:Immunophenotyping; D017730:Ki-1 Antigen / Q000276:immunology; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D008024:Ligands; D008214:Lymphocytes / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053278:OX40 Ligand; D011971:Receptors, Immunologic; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D048069:Tumor Necrosis Factors
D053330:4-1BB Ligand; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D053282:CD27 Ligand; D053285:CD30 Ligand; C505772:Cd70 protein, mouse; D007074:Immunoglobulin G; D017730:Ki-1 Antigen; D008024:Ligands; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D053278:OX40 Ligand; D011971:Receptors, Immunologic; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505717:Tnfrsf4 protein, mouse; C504586:Tnfsf4 protein, mouse; C505775:Tnfsf8 protein, mouse; C505975:Tnfsf9 protein, mouse; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors