Rag2R229Q hypomorph and ZAP70skg mouse models exemplify human partial T cell immunodeficiencies wherein CD4+ T cells were shown to be necessary for intestinal inflammation and arthritis, respectively (Marrella et al., 2007; Rigoni et al., 2016; Sakaguchi et al., 2003). Here, CD4 is linked to T-cell immunodeficiency.