While monocytes and macrophages have been shown to produce high levels of IL-6 during CRS26,27, CD4 CAR-T cells have been implicated as drivers of CRS through the activation of monocytes and the direct production of IL-626–30; however, CD8 CAR-T cells are more effective when supported by CD4 cell help29,31, and CAR-T cell product with defined CD4:CD8 ratio has been manufactured and showed reduced toxicity and improved disease-free survival32. This evidence concerns the gene CD8A and congenital rubella syndrome.