CD8⁺ T cell contraction is controlled by early inflammation¹

Student: 陳毓雯                         Time: 11/03/2004 14:00~15:00

Commentator: 陳舜華 老師               Place: Room 601

Abstract:

  Naïve CD8⁺ T cells can recognize antigen presented by MHC class I molecules through suitable costimulation and then rapidly proliferate and differentiate into primary effector T cells. Effector T cells can clear pathogen by killing infected cells or producing cytokines such as interferon-g (IFN-g) and tumor necrosis factor (TNF). After a rapid expansion phase, effector CD8⁺ T cell population undergoes a 90-95 % contraction and leave a stable memory cell pool, which can quickly and effectly eliminate pathogen in later infections. It is unclear which factors control the contraction and destine cells to become memory cells. In a previous study, treatment of mice with antibiotics 24 hours after infection by Listeria monocytogenes, substantially decreased the duration of infection and antigen display, but had minimal effects on the initiation or kinetics of CD8⁺ T cell contraction. This observation indicated that CD8⁺ T cell contraction is programmed by early events after infection and is not linked to pathogen clearance². Another study indicated that primary effector T cells expressing IL-7 receptor (IL-7R) tend to survive contraction to be memory cells³. In this article, the authors show that treatment with antibiotics in mice before L. monocytogenes infection allowed the development of functional antigen-specific memory CD8⁺ T cells in the absence of contraction. This phenomenon was associated to with a decreased inflammation and IFN-g production at the early stage of infection. Absence of contraction is also accompanied by an that increased fraction of antigen specific CD8⁺ cells expressing IL-7R at the peak of expansion. Thus, these results suggest that decreased early inflammation after infection may be beneficial for memory CD8⁺ T cells formation. This concept may prove useful in the design of vaccines against human infectious diseases.

References:

1.      Badovinac, V. P. et al. CD8⁺ T cell contraction is controlled by early inflammation. Nat. Immunol. 5, 809~817 (2004).

2.      Badovinac, V. P. et al. Programmed contraction of CD8+ T cells after infection. Nat. Immunol. 7, 619~626 (2002).

3.      Kaech, S.M. et al. Selective expression of the interlenkin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells. Nat Immunol. 4, 1191~1198 (2003).