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

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.