Killer T cells regulate antigen presentation for early expansion of memory, but not naive, CD8+ T cell.
Antigen presentation within the lymph node draining a site of infection is crucial for initiation of cytotoxic T cell responses. Precisely how this antigen presentation regulates T cell expansion in vivo is unclear. Here, we show that, in primary infection, antigen presentation peaks approximately 3 days postinfection and then slowly decays until day 12. This prolonged antigen presentation is required for optimal expansion of naive CD8(+) T cells, because early ablation of dendritic cells reduces the later CD8(+) T cell response. Antigen presentation during secondary infection was 10-fold lower in magnitude and largely terminated by day 4 postinfection. Expansion of memory, but not naive, antigen-specific T cells was tightly controlled by perforin-dependent cytolysis of antigen-presenting cells. The ability of the memory T cells to remove antigen-presenting cells provides a negative-feedback loop to directly limit the duration of antigen presentation in vivo.
Belz
Gabrielle T
GT
Division of Immunology, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne, Victoria 3050, Australia. belz@wehi.edu.au
Zhang
Lei
L
Lay
Matthew D H
MD
Kupresanin
Fiona
F
Davenport
Miles P
MP
D019264:Adoptive Transfer; D000704:Analysis of Variance; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000276:immunology; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin