Clonal Expansions of CD8(+) T Cells with IL-10 Secreting Capacity Occur during Chronic Mycobacterium tuberculosis Infection

Cyktor, Joshua C.; Carruthers, Bridget; Beamer, Gillian L.; Turner, Joanne

Using an Mtb-susceptible mouse strain, we reveal that CD8 + T cells that are capable of producing IL-10 can accumulate within the lung during Mtb infection. CD8 + T cells within the lung expressed CD69, indicative of activation and functional capacity, yet failed to show a concomitant enhancement of IFN-c-producing capacity. These findings indicate that highly activated CD8 + T cells within the lung have alternate function, which we show here to be the capacity to secrete IL-10, measured by ELISPOT due to the known difficulties of measuring IL-10 by intracellular flow cytometry. Altered function was associated with the co-expression of a variety of receptors know for negative regulation of cell function (PD-1, CD122, Tim-3) [25, 28, 33, 34] . In support of our findings, previous studies have shown that in chronic murine Mtb infection PD-1 + T cells can proliferate but fail to secrete IFN-c unless this inhibition is overcome by direct TcR stimulation [45, 46] . It is unclear at this time why CD8 + T cells with inhibitory properties arise in CBA/J mice as Mtb infection progresses but we can hypothesize that this is a consequence of enhanced immune activation and subsequent exhaustion due to increasing bacterial loads in this mouse strain (Fig. 1) [4, 6] .