T Cell Defects

T cells play the central role in adaptive immunity and deficiencies affecting this key component of the immune system result in the most severe forms of primary immunodeficiency. The classic example within this group of immunodeficiencies is severe combined immunodeficiency (SCID). The infectious complications include a wide spectrum of organisms, but viral infections and opportunistic infections are commonly found in infants with SCID who are not identified by newborn screening (NBS). With NBS for SCID through quantification of T cell receptor excision circles (TRECs), the prognosis associated with this condition has improved considerably, with the vast majority of these infants in the USA found early and often without infectious complications. Conditions of T cell immunity not as severe as SCID are broad, and, in addition to infection, noninfectious complications can develop including lymphoproliferation, inflammation, and autoimmunity, notably inflammatory bowel disease. The relatively poor prognosis of T cell immune deficiencies requires those affected to initiate extensive antimicrobial prophylaxis often combined with immunosuppressive treatments to control inflammatory complications. Definitive therapy often includes hematopoietic cell transplant. There are nearly 90 primary immunodeficiency conditions that are considered predominantly T cell and combined T cell and B cell conditions, not all of which can be covered in the scope of this chapter (Picard et al., J Clin Immunol. 35(8):696–726, 2015). Instead we will focus on severe combined immunodeficiency (SCID) in its various forms as well as highlight specific immune defects that illustrate unique aspects of aberrant T cell immunity and resultant clinical manifestations.