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

We examined the number of T cells that were capable of secreting IFN-c after ex vivo TcR stimulation. As expected, C57BL/6 mice had increasing numbers of CD4 + [4] and CD8 + T cells that could produce IFN-c as infection progressed (Fig. 2a) , which paralleled the increasing numbers of T cells within the lung (Fig. 1) . CBA/J showed an equivalent increase in IFN-cproducing CD4 + T cells (Fig. 2b) , albeit at a significantly lower number compared to C57BL/6, as we have previously described [3, 4] . Where the data differed, however, was in the finding that the number of IFN-c-producing CD8 + T cells reached a plateau as early as day 30 post-infection and did not increase any further, despite a significant accumulation of CD8 + T cells within the lungs of CBA/J mice. As Mtb infection progressed we also observed a significant increase in the number of CD8 + T cells from CBA/J mice that could express CD69 (Fig. 2c) , with over 40% of all CD8 + T cells in the lungs of CBA/J mice being activated during chronic infection. CD8 + T cells also expressed the suppressor of T H 1 responses Tim-3 (Fig. 2d) , PD-1 (Fig. 2e) , with a small population expressing both PD-1 and CD122 (Fig. 2f) . Therefore, although highly activated, a proportion of CD8 + T cell expansions from chronic Mtb infected CBA/J mice had a phenotype that was not associated with T H 1 cytokine secretion but was instead linked to immuno-suppressive properties including IL-10 production [34] . Because IL-10 production has been closely linked to Mtb susceptibility of CBA/J mice [5] , we next examined the capacity of CD8 + T cells to produce IL-10.