The bacille Calmette–Guérin vaccine provides very efficient protection in standard animal models of Mycobacterium tuberculosis challenge. We show in this article that although bacille Calmette–Guérin controlled M. tuberculosis growth for 7 wk of infection, the protection was gradually lost as the infection entered the chronic phase. The regrowth of M. tuberculosis coincided with an almost complete disappearance of IL-2–producing CD4 T cells. Booster vaccination with a subunit vaccine (Ag85B-ESAT-6+CAF01) expanded IL-2+ CD4+ T cell coexpressing either TNF-α or TNF-α/IFN-γ, and the maintenance of this population in the late stage of infection was associated with enhanced control of bacterial growth. The IL-2+ CD4+ T cell subsets were KLRG1− (nonterminally differentiated), were found to be CD62Lhigh, and further maintained a pronounced proliferative and cytokine-producing potential in the draining lymph nodes, when the animals were challenged 2 y postvaccination. These results suggest that the CD4+ KLRG1− IL-2–secreting subsets are central memory T cells with the potential to continuously replenish the T cells at the site of infection and prevent attrition and functional exhaustion.
This work was supported by European Commission Contract FP7-HEALTH-F3-2009-241745 under the NEWTBVAC consortium and through the ADITEC consortium supported by the European Commission through Contract FP7-HEALTH-2011.1.4-4-280873.
- Received January 25, 2013.
- Accepted April 12, 2013.
- Copyright © 2013 by The American Association of Immunologists, Inc.