CD4 and HIV infectious disease: While the antigenic stimulation noted with aging, SARS-CoV-2, and HIV infection was associated with CD4+ T-cell lymphopenia, the lymphopenia associated with aging (Supplementary Fig. 9; Supplementary Note 6) and COVID-19 occurs mainly within the context of subgrades tracking CD8-CD4 equilibrium (e.g., IHG-IIb and IHG-IIc; Fig. 6b–c, e).