Clonal immune responses of Mycobacterium-specific gammadelta T cells in tuberculous and non-tuberculous tissues during M. tuberculosis infection
journal contributionposted on 21.08.2012, 00:00 authored by Dan Huang, Crystal Y. Chen, Meihong Zhang, Liyou Qiu, Yun Shen, George Du, Keyuan Zhou, Richard Wang, Zheng W. Chen
Background: We previously demonstrated that unvaccinated macaques infected with large-dose M.tuberculosis(Mtb) exhibited delays for pulmonary trafficking of Ag-specific alphabeta and gammadelta T effector cells, and developed severe lung tuberculosis(TB) and "secondary" Mtb infection in remote organs such as liver and kidney. Despite delays in lungs, local immunity in remote organs may accumulate since progressive immune activation after pulmonary Mtb infection may allow IFNgamma-producing gammadelta T cells to adequately develop and traffic to lately-infected remote organs. As initial efforts to test this hypothesis, we comparatively examined TCR repertoire/clonality, tissue trafficking and effector function of Vgamma2Vdelta2 T cells in lung with severe TB and in liver/kidney without apparent TB. Methodology/Principal Findings: We utilized conventional infection-immunity approaches in macaque TB model, and employed our decades-long expertise for TCR repertoire analyses. TCR repertoires in Vgamma2Vdelta2 T-cell subpopulation were broad during primary Mtb infection as most TCR clones found in lymphoid system, lung, kidney and liver were distinct. Polyclonally-expanded Vgamma2Vdelta2 T-cell clones from lymphoid tissues appeared to distribute and localize in lung TB granuloms at the endpoint after Mtb infection by aerosol. Interestingly, some TCR clones appeared to be more predominant than others in lymphocytes from liver or kidney without apparent TB lesions. TCR CDR3 spetratyping revealed such clonal dominance, and the clonal dominance of expanded Vgamma2Vdelta2 T cells in kidney/liver tissues was associated with undetectable or low-level TB burdens. Furthermore, Vgamma2Vdelta2 T cells from tissue compartments could mount effector function for producing anti-mycobacterium cytokine. Conclusion: We were the first to demonstrate clonal immune responses of mycobacterium-specific Vgamma2Vdelta2 T cells in the lymphoid system, heavily-infected lungs and lately subtly-infected kidneys or livers during primary Mtb infection. While clonally-expanded Vgamma2Vdelta2 T cells accumulated in lately-infected kidneys/livers without apparent TB lesions, TB burdens or lesions appeared to impact TCR repertoires and tissue trafficking patterns of activated Vgamma2Vdelta2 T cells.