Provided herein are novel methods for increasing T cell effector function in a T cell populations, as well as methods for increasing T cell effector function in a subject. The methods include contacting a T cell in a T cell population with a pharmaceutical composition comprising an antagonist of histone deacetylase 3 (HDAC3). Also provided herein are methods for identifying a compound that modulates HDAC3 activity in cytotoxic T cells.