Abstract: The present invention relates generally to binding agents useful in the selective depletion of T cells in vivo. More specifically, the invention relates to ICOS-binding agents which once bound to ICOS expressed on the surface of cells, in particular ICOS-bearing activated T cells, result in the in vivo depletion of cells to which they are bound. Methods of treating T cell related diseases using said ICOS-binding agents, and pharmaceutical compositions comprising said ICOS-binding agents, a method of identifying an ICOS-binding agent, and monoclonal anti-ICOS antibodies capable of eliminating cells in vivo which express ICOS on their surface are also provided.