Recent advances in understanding the pathophysiology of primary T cell immunodeficiencies

•Many monogenic immunodeficiencies have been identified.•Mechanistic findings pave the way for targeted therapeutic interventions.

Primary immunodeficiencies (PIDs) constitute a large group of rare disorders that affect the function of the immune system. These deficiencies are usually associated with inability to prevent infections but can also result in allergy, inflammation, autoimmunity, and cancer. The recent characterization of many different monogenic defects has shed light on a range of non-redundant differentiation, effector, and regulatory functions of immune cells. The present review focuses on PIDs that affect adaptive immunity in general and T lymphocytes in particular. The analysis of PIDs is now opening up new pathways towards targeted therapies.