A malaria-naïve person therefore, develops protection against natural challenge when rapid cross-presentation of exogenous MHC I, and all MHC II antigen presentation, and consequently also, major sources of rapid antigen-specific activation and de novo induction of tolerogenic CD4+ and CD8+ regulatory T cells in the skin and skin-draining LN, are blocked at the skinstage during immunizing skin infections. Here, CD4 is linked to malaria.