title: Critical role of activation-inducible lymphocyte immunomediatory molecule/inducible costimulator in the effector function of human T cells: a comparative in vitro study of effects of its blockade and CD28 blockade in human beings and monkeys.
abstract: Activation-inducible lymphocyte immunomediatory molecule (AILIM; also referred to as inducible costimulator, ICOS) is the third homolog of the "professional" costimulatory molecule, CD28. To date, the characteristics and role of AILIM/ICOS, especially in effector function of T cells, have been determined through numerous studies in vitro and in vivo using mice. Considering potential differences among species, whether the AILIM/ICOS blockade acts as an efficacious immunomodulator for human diseases remains to be elucidated. In the present study, ability of AILIM/ICOS blockade to modulate immune responses of human and monkey cells was investigated using a fully human antibody (JTA-009), comparing the effect of CD28 blockade. JTA-009 blocked the response of human and monkey T cells co-stimulated with anti-CD3 and AILIM/ICOS ligand, B7h. AILIM/ICOS and CD28 blockade both inhibited human mixed lymphocyte reaction in different fashions, as well as cytokine production in T helper (Th) 1-/Th2-type recall responses. In monkeys however, CD28 blockade by CTLA4-Ig effectively prevented mixed lymphocyte reaction to a greater extent than AILIM/ICOS blockade. These results suggest that AILIM/ICOS blockade is valuable for suppressing both primary allogenic response and recall responses of T cell in human beings, and that there are differences between human and monkey use preferences for costimulatory molecules.
authors.affiliation: Biological and Pharmacological Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., Takatsuki, Osaka, Japan. nobuyuki.tajima@ims.jti.co.jp
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Tajima
authors.forename: Katsunari
authors.initials: K
authors.lastname: Tezuka
authors.forename: Masaru
authors.initials: M
authors.lastname: Tanaka
authors.forename: Minako
authors.initials: M
authors.lastname: Tanimoto
authors.forename: Atsuko
authors.initials: A
authors.lastname: Miyai
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takeshima
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D000882:Haplorhini; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D019138:Antibodies, Blocking; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; C556692:ICOS protein, human; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein