SKG mice have reduced T cell receptor (TCR) signal strength and thymic selection (7, 8), functionally impaired Foxp3+ Tregs, Th17-skewed autoreactive CD4+ T cells, mild systemic CD4 and CD8 T lymphopenia (9) and depleted ileal cytotoxic T cells, reflecting T cell immunodeficiency for bacterial control and dysfunctional inflammatory regulation. Here, CD4 is linked to immunodeficiency disease.