The apparent failure of this approach in our newly established mouse model of progression from LTBI to active TB could be due to the following non-mutually exclusive explanations: (i) transient expansion of non-CD4 cell populations after IL-2/anti-IL-2 treatment; (ii) requirement of prophylactic rather than preventive expansion of cell populations; (iii) activation of a pro-inflammatory cytokine ‘storm’ that supports rather than limits initial Mtb replication; and (iv) toxic side effects of high doses of IL-2, such as vascular leakage syndrome [35], promoting Mtb spread. The gene discussed is IL2; the disease is tuberculosis.