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 addition to IL-10 production, we also observed that CD8 + T cells from CBA/J mice had severely restricted diversity of their TcR repertoire which would significantly limit the breadth of antigens that CBA/J CD8 + T cells can recognize. CBA/J mice have an endogenous mouse mammary tumor virus (MTV-6) that selectively deletes various TcR Vb chains such as Vb8.1, and Vb 17a [50, 51] however this alone is not sufficient to explain the limited TcR diversity in CBA/J mice. It is possible that Mtb infection leads to specific deletion of certain subsets of protective CD8 + T cells or is driving clonal expansion of less protective cells (Vb8, Vb14). Alternatively Vb8/Vb14 CD8 + T cells in CBA/J mice may respond to a dominant Mtb antigen(s) expressed in vivo, where persistent responsiveness leads to immune exhaustion and subsequent regulation through receptors such as PD-1 and Tim-3. Clonal CD8 + expansions have been described in TB patients [52] , including pediatric TB [42] , supporting the relevance of our findings to TB in man. Clonal CD8 + expansions are also common in the elderly and in many viral models [42, 43, [53] [54] [55] [56] [57] [58] , yet their importance in Mtb infection is still unclear.