Regulation of neuronal plasticity by the immune system is an evolving field of modern neuroscience. Here we employ immune deficient mice to examine the role of the immune system in learning behavior of mice in a variety of cognitive tasks. While no motivation or motor function deficits are evident in severe combined immune deficient (scid) mice, there was significant impairment in acquisition of cognitive tasks as compared to wild-type (WT) control mice. Moreover, acute depletion of adaptive immunity in adult WT mice significantly impaired learning behavior. Passive transfer of autologous T cells into WT mice following ablation of adaptive immunity restored previously impaired cognitive function. These results suggest that throughout lifetime, immune system supports cognitive function and may therefore have far-reaching therapeutic implications for cognitive disorders.