CD4 and infection: For example, notwithstanding any putative evolutionary advantage conferred by cytokine “priming” of naïve CD4+ T cells in the context of infection (34), even temporary IL-6 signal-blockade during the preclinical phase of RA—conceivably tailored to target the trans pathway specifically (35), —could reverse transcriptional imprinting in a time-critical manner and favorably augment subsequent disease progression in an identifiable subgroup of patients.