Distinct differences in the expansion and phenotype of TB10.4 specific CD8 and CD4 T cells after infection with Mycobacterium tuberculosis.
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.
Hoang
Truc Thi Kim Thanh
TT
Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
Nansen
Anneline
A
Roy
Sugata
S
Billeskov
Rolf
R
Aagaard
Claus
C
Elvang
Tara
T
Dietrich
Jes
J
Andersen
Peter
P
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
D000942:Antigens, Bacterial; C501710:TB10.4 antigen, Mycobacterium tuberculosis