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

Our failure to observe any significant change in CFU following CD8 + or Vb8 + T cell depletion can be interpreted in several ways, the simplest being that IL-10-producing CD8 + T cells have no biological influence on the control of Mtb infection. While this is a possibility, we would reason that at the least the presence of IL-10producing CD8 + T cells can be a putative biomarker of TB disease progression as they are only observed in a mouse strain of Mtb susceptibility, and IL-10 producing T cells have been previously described in the blood of TB patients [37] . In support of a negative role for CD8 + T cells in CBA/J mice, in vivo depletion led to a moderate, albeit not significant, decrease in CFU. Thus is in contrast to CD4 + T cell depletion in which all the mice were either dead or moribund before the necropsy time point (data not shown). These findings indicate that some CD8 + T cells from CBA/J mice fail to contribute to protection in a similar manner than might be expected from studies of other mouse strains [47] [48] [49] . One possibility for our failure to detect significant changes in CFU following CD8 + T cell depletion is our observation that CD8 + T cells can secrete both IL-10 and IFN-c. Depletion of all CD8 + T cells would also remove a protective population, leading to a neutral effect. Previous studies from our laboratory have shown that blocking the action of IL-10 in CBA/J mice during Mtb infection provides enhanced protection [5] , and we consider that blocking the action of IL-10 from IL-10/IFN-c-secreting CD8 + T cells contributed to this phenotype.