Impairment of antigen-presenting cell function in mice lacking expression of OX40 ligand.
OX40 expressed on activated T cells is known to be an important costimulatory molecule on T cell activation in vitro. However, the in vivo functional significance of the interaction between OX40 and its ligand, OX40L, is still unclear. To investigate the role of OX40L during in vivo immune responses, we generated OX40L-deficient mice and a blocking anti-OX40L monoclonal antibody, MGP34. OX40L expression was demonstrated on splenic B cells after CD40 and anti-immunoglobulin (Ig)M stimulation, while only CD40 ligation was capable of inducing OX40L on dendritic cells. OX40L-deficient and MGP34-treated mice engendered apparent suppression of the recall reaction of T cells primed with both protein antigens and alloantigens and a significant reduction in keyhole limpet hemocyanin-specific IgG production. The impaired T cell priming was also accompanied by a concomitant reduction of both T helper type 1 (Th1) and Th2 cytokines. Furthermore, antigen-presenting cells (APCs) derived from the mutant mice revealed an impaired intrinsic APC function, demonstrating the importance of OX40L in both the priming and effector phases of T cell activation. Collectively, these results provide convincing evidence that OX40L, expressed on APCs, plays a critical role in antigen-specific T cell responses in vivo.
Murata
K
K
Department of Microbiology and Immunology, Tohoku University School of Medicine, Sendai 980-8575, Japan.
Ishii
N
N
Takano
H
H
Miura
S
S
Ndhlovu
L C
LC
Nose
M
M
Noda
T
T
Sugamura
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003470:Culture Media; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016130:Immunophenotyping; D007519:Isoantigens / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053278:OX40 Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D048069:Tumor Necrosis Factors
D000911:Antibodies, Monoclonal; D003470:Culture Media; D016207:Cytokines; D007519:Isoantigens; D008562:Membrane Glycoproteins; D053278:OX40 Ligand; D018124:Receptors, Tumor Necrosis Factor; C504586:Tnfsf4 protein, mouse; D048069:Tumor Necrosis Factors