Effector memory T-cells dominate immune responses in tuberculosis treatment: antigen or bacteria persistence?

To compare ex vivo immunological responses upon stimulation of lymphocytes with Mycobacterium tuberculosis-specific antigens in three groups: 1) subjects diagnosed with tuberculosis (TB) in the early 1940s and 1950s but who did not receive anti-tuberculosis chemotherapy (n = 5), 2) subjects treated with anti-tuberculosis agents prior to the rifampicin (RMP) era (n = 26) and 3) subjects who received RMP as a part of modern combination therapy (n = 7).

A total of 38 healthy subjects, mean age 70 +/- 13 years, with a history of previously treated TB were recruited. Peripheral blood mononuclear cells were collected and analysed as a batch by ELISpot. Representative samples with high reactivities were further immunophenotypically characterised.

No differences between the studied groups were detected with regard to the frequencies of reactive lymphocytes. The dominant immunophenotypic profile of the representative responders, irrespective of the treatment schemes, was CD4+CD45RO+CD45RA-CD27-CD28-CCR7-, compatible with the fast reacting effector memory T-cell lineage (T(EM)).

Specific T(EM) cells persist even in subjects treated for TB decades ago with modern anti-tuberculosis chemotherapy. Additional studies are needed to address the question of what drives the survival of T(EM) after adequate treatment: persistence of antigens or bacteria.