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

In this study we show that Mtb-susceptible CBA/J mice accumulated large numbers of CD8 + T cells in their lungs as Mtb infection progressed that could not be fully accounted for by an expansion of IFN-c-producing CD8 + T cells. CD8 + T cell expansions expressed the inhibitory molecules PD-1, Tim-3, and/ or CD122, and were capable of secreting IL-10. CD8 + T cells from CBA/J mice also preferentially expressed TcR Vb8 and Vb14, severely limiting the diversity of the CD8 + T cell repertoire. Although Vb8 CD8 + T cells could secrete IL-10, in vivo depletion of this specific T cell clonal population during chronic infection did not overtly change the Mtb burden in the lungs in the timeframe tested, although the amount of IL-10 in the lung was reduced indicating some biological impact of depletion. Comparing mouse strains that are relatively resistant and susceptible to Mtb has enabled us to uncover a previously unappreciated role for CD8 + T cells in Mtb susceptibility, and links the poor T cell function previously described by us [4, 6, 36] with increased production of IL-10 in the CBA/J mouse strain.