No life without death--apoptosis as prerequisite for T cell activation.
The orchestrated death of infected cells is key to our understanding of CD8 T cell activation against pathogens. Most intracellular bacteria including Mycobacterium tuberculosis, the etiologic agent of tuberculosis, remain enclosed in phagosomes of infected macrophages. CD8 T cells play a critical role in defense of infection and recognize antigens originating from the cytosol presented by MHC-I molecules. Since mycobacteria do not gain access to the cytosolic MHC-I presentation pathway, the fundamental question as to how CD8 T cells encounter mycobacterial antigens remains to be solved. In this review, we focus on solutions for this enigma and describe the detour pathway of T cell activation. Mycobacteria induce cell death of infected macrophages which thereby leave a last message by releasing apoptotic vesicles. Subsequently, these antigen-containing entities are engulfed by dendritic cells which process the mycobacterial cargo for efficient antigen presentation and CD8 T cell activation. Since the dying infected cell is the origin of a protective T cell response destined to preserve life and individuality, the detour pathway represents an altruistic principle at a cellular level which corresponds to the macroscopic world where death is the precondition to perpetuate the living.
Winau
F
F
Max-Planck-Institute for Infection Biology, Department of Immunology, Schumannstr. 21-22, D-10117 Berlin, Germany. winau@mpiib-berlin.mpg.de
Hegasy
G
G
Kaufmann
S H E
SH
Schaible
U E
UE
D000818:Animals; D017209:Apoptosis; D045142:Cross-Priming / Q000276:immunology; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000382:microbiology