Requirement for CD4 T cell help in generating functional CD8 T cell memory

Science. 300: 337-339, 2003.

Speaker: 吳怡靜                           Date: PM 2:00-3:00; 12/31/2003

Commentator: 余俊強 老師                  Room: 601

Abstract:

    Memory lymphocytes provide long-term protection in response to infections or immunization. The long-term defense contributed by memory CD8 T cells depends on their ability to increase their numbers rapidly and exert potent effector responses and their ability to persist for long periods through homeostatic proliferation (1). In previous studies, the CD4 T cells stimulate APCs via recognizing antigens on APCs surface. The stimulated APCs in turn activate CD8 T cells (2). In addition, CD4 T cells provide help by secreting key cytokines for B cell and CD8 T cell responses.The memory CD8 T cells were generated in smaller number during acute viral and bacterial infections in CD4-deficient animals (3). In this article, authors compared responses between “helped” and “unhelped” memory CD8 T cells in vivo, and demonstrated the qualitative effect of CD4 help on memory CD8 T cell responses. Primary infection induced similar memory CD8 T cell responses in CD4^+/+ and CD4^-/- mice. However, after secondary infection, memory CD8 T cells in CD4^+/+ mice mounted a significant stronger recall response than did in CD4^-/- mice. Furthermore, CD4 T cells are required for the generation of memory CD8 T cell capable of efficient recall response during the priming phase, whereas they are not for secondary expansion in the boosting phase. Knowledge about mechanism how CD4 T cells help CD8 T cells will facilitate designing vaccines to generate the most long-lasting and efficacious CD8T cell protection.

References:

1.      Kaech SM, et al. CD8 T cells remember with a little help. Science 300: 263-265, 2003.

2.      den Haan JMM, et al. A novel helper role for CD4 T cells. Proc. Natl. Acad. Sci. U.S.A. 97: 12950-12952, 2000.

3.      Shedlock DJ, et al.. Role of CD4 T Cell Help and Costimulation in CD8 T Cell Responses During Listeria monocytogenes Infection. J. Immunol. 170: 2053-2063, 2003.