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 chronic viral infection models, CD8 + T cells can become dysfunctional after chronic antigenic stimulation, characterized by a lack of functional or proliferative capability, secretion of IL-10 [22] [23] [24] and surface expression of inhibitory molecules, such as programmed cell death-1 (PD-1) and T cell immunoglobulin and mucin protein-3 (Tim-3) [25, 26] . PD-1 has classically been used as a marker of T cell exhaustion in viral infection and in cancer [27] [28] [29] [30] , while other studies have found that cells expressing Tim-3 are dysfunctional and lack regulation [31, 32] , and that coexpression of PD-1 and Tim-3 leads to extensive dysfunction of CD8 + T cells [33] . Furthermore, CD8 + T cells expressing both PD-1 and CD122 (the b subunit of the IL-2 receptor) have been shown to have suppressive qualities and secrete IL-10 [34] . We, and others, have previously demonstrated that Mtb susceptibility in CBA/J mice is mediated by excessive pulmonary IL-10 during infection [1, 2, 5, 35, 36] , yet the underlying mechanism remains unclear. Although numerous cell types are capable of producing IL-10, studies have previously shown that IL-10-producing T cells can actively suppress the immune response in TB patients [37] , supporting an investigation into the IL-10-producing properties of CD8 + T cells during Mtb infection in CBA/J mice.