distinct differences in the expansion and phenotype of tb10.4 specific cd8 and cd4 t cells after infection with mycobacterium tuberculosis明显的扩张和表型的差异tb10.4特定cd8和cd4 t细胞在感染结核分枝杆菌.pdfVIP

Distinct Differences in the Expansion and Phenotype of TB10.4 Specific CD8 and CD4 T Cells after Infection with Mycobacterium tuberculosis 1 2 1 1 1 Truc Thi Kim Thanh Hoang , Anneline Nansen , Sugata Roy , Rolf Billeskov , Claus Aagaard , Tara 1 1 1 Elvang , Jes Dietrich *, Peter Andersen * ˚ 1 Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark, 2 Department of Immunopharmacology, Novo Nordisk, Maløv, Denmark Abstract Background: Recently we and others have identified CD8 and CD4 T cell epitopes within the highly expressed M. tuberculosis protein TB10.4. This has enabled, for the first time, a comparative study of the dynamics and function of CD4 and CD8 T cells specific for epitopes within the same protein in various stages of TB infection. Methods and Findings: We focused on T cells directed to two epitopes in TB10.4; the MHC class I restricted epitope TB10.4 3–11 (CD8/10.4 T cells) and the MHC class II restricted epitope TB10.4 74–88 (CD4/10.4 T cells). CD4/10.4 and CD8/10.4 T cells displayed marked differences in terms of expansion and contraction in a mouse TB model. CD4/10.4 T cells dominated in the early phase of infection whereas CD8/10.4 T cells were expanded after week 16 and reached 5–8 fold higher numbers in the late phase of infection. In the early phase of infection both CD4/10.4 and CD8/10.4 T cells were characterized by 20–25% polyfunctional cells (IL-2+ + + , IFN-c , TNF-a ), but whereas the majority