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 have demonstrated that clonal expansions of CD8 + T cells from CBA/J mice accumulate in the lung over the course of Mtb infection. This accumulation did not yield an equivalent increase in IFN-c + CD8 + T cells and, upon further phenotypic examination, we discovered that highly activated CD8 + T cells from CBA/J mice expressed the T cell dysfunction markers PD-1 and Tim-3, as well as co-expression of PD-1 and CD122 suggesting possible immunosuppressive activity. After ex vivo purification and culture, it was shown that CD8 + T cells from CBA/J mice were capable of secreting IL-10 after TcR stimulation and in response to Mtb infected BMDCs. Depletion of Vb8 + cells or the entire CD8 + T cell population in Mtb-infected CBA/J mice led to a significant reduction in pulmonary IL-10 levels, however, we observed no significant change in pulmonary CFU.