Methods and compositions for treating an infection or
disease that results from (1) failure to elicit rapid
T cell mediated responses, (2) induction of
T cell exhaustion,
T cell anergy or both, or (3) failure to activate monocytes, macrophages, dendritic cells and / or other APCs, for example, as required to kill
intracellular pathogens. The method and compositions solve the problem of undesired T
cell inhibition by binding to and blocking PD-1 to prevent or reduce inhibitory
signal transduction, or by binding to ligands of PD-1 such as PD-L1, thereby preventing (in whole or in part) the ligand from binding to PD-1 to deliver an inhibitory
signal. The immune response can be modulated by providing antagonists which bind with different affinity (i.e., more or less as required), by varying the dosage of agent which is administered, by
intermittent dosing over a regime, and combinations thereof, that provides for dissociation of agent from the molecule to which it is bound prior to being administered again (similar to what occurs with
antigen elicitation using priming and boosting). In some cases it may be particularly desirable to stimulate the
immune system, then remove the stimulation.