In a study using an ex vivo model of tonsillar HIV infection and in vivo model of simian immunodeficiency virus infection in rhesus macaques, virus infection was associated with an expansion of suppressive CD4+ TFR cells, expressing increased levels of co-inhibitory receptors CTLA-4 and lymphocyte-activation gene 3 (LAG-3), and increased production of anti-inflammatory cytokines IL-10 and TGF-β [170]. Here, CD4 is linked to HIV infectious disease.