Minimal activation of memory CD8⁺ T cell by tissue derived dendritic cells favors the stimulation of naïve CD8⁺ T cells

Speaker: 蔡明勳                    Time: 13:00-14:00, 10/17, 2007

Commentator: 陳舜華 老師           Place: Room 601

Abstract

  CTL priming is an important event in viral infection and requires antigen presentation by dendritic cells (DC). The classic model of DC function shows that DC can capture antigen in peripheral tissue and transport this to draining lymph nodes (LNs). In recent evidences, the DCs present in lymph nodes can be divided into lymph node-resident DCs (or blood-derived DCs) and tissue-derived DCs (or migratory DCs). Besides, it has been reported that induction of naïve and memory CD8⁺ T cells response depends largely on antigen presentation by a single subset of lymph node-resident DCs, the CD8α⁺ DCs. However, In previous studies, the authors found an lung-derived DC subset, CD8α^－CD11b^－ DCs, also presented class I-restricted viral antigen during acute lung infection. Moreover, these lung-derived cells could act as a source of antigen for transfer to the lymph node-resident population. To examine whether the tissue-derived DC subset might be capable of priming naïve CD8 T cells and initiating secondary responses by memory T cells, the antigen-specific gBT-I naïve and memory CD8 T cells have been generated. Although memory CD8 T cells have been reported to have less-stringent requirements for activation than naïve T cell, the authors found memory T cells were poorly responsive to tissue-derived CD8α^－ DCs unexpectedly. Further, they showed the basis for poor memory responses in reduced capacity of tissue-derived CD8α^－ DCs to memory T cells. In addition, tissue-derived CD8α^－ DCs not only remain longer antigen presentation but “favor” to stimulate naïve CD8 T cells. The mechanism may provide a insight for inducing naïve responses in a dominant but ineffective memory responses. If such dominant memory responses are nonprotective to persistent infection, then subdominant naïve T cells may be given a late opportunity to respond and to provide protection. In addition, the reduction capacity of tissue- derived DCs stimulating memory might mean that most natural stimuli are ineffective at stimulating memory T cells.   

Reference

1.      Belz GT, Bedoui S, Kupresanin F, Carbone FR, Heath WR. 2007. Minimal activation of memory CD8(+) T cell by tissue-derived dendritic cells favors the stimulation of naive CD8(+) T cells. Nat. Immunol. 8(10):1060-1066.

2.      Belz GT, Smith CM, Kleinert L, Reading P, Brooks A, Shortman K, Carbone FR, Heath WR. 2004. Distinct migrating and nonmigrating dendritic cell populations are involved in MHC class I-restricted antigen presentation after lung infection with virus. Proc. Natl. Acad. Sci. 101(23):8670-8675.