title: Distinct differences in the expansion and phenotype of TB10.4 specific CD8 and CD4 T cells after infection with Mycobacterium tuberculosis.
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.
  
  
  RESULTS
  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-gamma(+), TNF-alpha(+)), but whereas the majority of CD4/10.4 T cells were maintained as polyfunctional T cells throughout infection, CD8/10.4 T cells differentiated almost exclusively into effector cells (IFN-gamma(+), TNF-alpha(+)). Both CD4/10.4 and CD8/10.4 T cells exhibited cytotoxicity in vivo in the early phase of infection, but whereas CD4/10.4 cell mediated cytotoxicity waned during the infection, CD8/10.4 T cells exhibited increasing cytotoxic potential throughout the infection.
  
  
  CONCLUSIONS
  Our results show that CD4 and CD8 T cells directed to epitopes in the same antigen differ both in their kinetics and functional characteristics throughout an infection with M. tuberculosis. In addition, the observed strong expansion of CD8 T cells in the late stages of infection could have implications for the development of post exposure vaccines against latent TB.
authors.affiliation: Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Truc Thi Kim Thanh
authors.initials: TT
authors.lastname: Hoang
authors.forename: Anneline
authors.initials: A
authors.lastname: Nansen
authors.forename: Sugata
authors.initials: S
authors.lastname: Roy
authors.forename: Rolf
authors.initials: R
authors.lastname: Billeskov
authors.forename: Claus
authors.initials: C
authors.lastname: Aagaard
authors.forename: Tara
authors.initials: T
authors.lastname: Elvang
authors.forename: Jes
authors.initials: J
authors.lastname: Dietrich
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000096:biosynthesis* / Q000737:chemistry; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000382:microbiology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000382:microbiology*; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D010641:Phenotype
chemical_list: D000942:Antigens, Bacterial; C501710:TB10.4 antigen, Mycobacterium tuberculosis