Multifunctional T cells have been shown to be protective in chronic viral infections. However, in mycobacterial infections evidence for a protective role of multifunctional T cells remains inconclusive. Short-term cultures of peripheral blood mononuclear cells stimulated with the early-infection phase induced Mycobacterium tuberculosis (Mtb) RD-1 antigens ESAT6/CFP10 have been mainly used to assess T cell multifunctionality and long-term culture assays have been proposed to be more sensitive than short-term assays to assess memory T-cells, which are essential for long-term immunity. Here, we have used a long-term culture assay system to study the T-cell immune response to the Mtb latency-associated DosR and reactivation Rpf antigens, compared to ESAT6/CFP10, in patients with pulmonary TB (PTB) and household contacts of PTB, long-term latently infected individual (ltLTBI), from an endemic community. Our results show that the DosR encoded Rv1737c (narK2) and Rv2029c (pfkB), and Rv2389c (RpfD) antigens of M. tuberculosis induced a higher frequency of CD4(+) or CD8(+) mono- or bi- (but not triple) -functional T cells producing IFNγ and/or TNFα in ltLTBI compared to PTB. Moreover, the frequency of CD4(+) and/or CD8(+) T cells with a CD45RO(+)CD27(+) phenotype was higher in ltLTBI compared to PTB. Thus, the immune response to selected DosR and Rpf antigens may be associated with long-term latency, correlating with protection from Mtb reactivation in ltLTBI. Further study of the functional and memory phenotypes may contribute to discriminate further between the different states of Mtb infection.
Multifunctional T cell response to DosR and Rpf antigens is associated with protection in long-term M. tuberculosis-infected individuals in Colombia.