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 determined the clonal repertoire of the CD8 + T cells that accumulated in the lungs of CBA/J mice during Mtb infection to determine whether the reactivity of CD8 + T cells was potentially driven by a dominant antigen, a concept supported by the finding of T cell clonal expansions in TB patients [42, 43] . At late stages of Mtb infection, we observed that CD8 + T cells from CBA/J mice primarily expressed two variable regions of the TcR beta chain (Vb). Vb8 (8.2,8.3) and Vb14 were expressed by approximately 45% of all CD8 + T cells in CBA/J mice at day 120 after Mtb infection, compared to a less restrictive repertoire in C57BL/6 mice (Fig. 4a) . Vb expression was comparable on CD4 + T cells from both mouse strains (Fig. 4b) , indicating a unique expansion within the CD8 + T cell pool in CBA/J mice as Mtb infection progressed. More detailed examination over the course of Mtb infection showed that the percentage of CD8 + T cells expressing Vb8 or Vb14 was always significantly higher throughout Mtb infection in CBA/J mice, and this population significantly expanded further at late time points of Mtb infection (Fig. 4c, d) . Similar to our findings with CD8 + T cell expansions, we found that both Vb8 and Vb14 CD8 + T cells were highly activated (Fig. 4e) .