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

• Published in: Human immunology 2008-07, Vol.69 (7), p.399-408
• Main Authors: Tajima, Nobuyuki, Tezuka, Katsunari, Tanaka, Masaru, Tanimoto, Minako, Miyai, Atsuko, Takeshima, Hiroaki, Watanabe, Yoshihiro
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Animals; Antibodies, Blocking - immunology; Antigens, Differentiation, T-Lymphocyte - immunology; CD28; CD28 Antigens - immunology; Costimulatory molecule; Cytotoxicity, Immunologic; Haplorhini; Human; Humans; ICOS; Inducible T-Cell Co-Stimulator Protein; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Mice; Monkey; Species Specificity; T-Lymphocyte Subsets - immunology
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2008.05.002

Summary 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.