Memory CD8+ T cell responses expand when antigen presentation overcomes T cell self-regulation

Ian A. Cockburn, Sumana Chakravarty, Michael G. Overstreet, Adolfo García-Sastre, Fidel Zavala

Research output: Contribution to journalArticle

Abstract

Antimicrobial memory CD8+ T cell responses are not readily expanded by either repeated infections or immunizations. This is a major obstacle to the development of T cell vaccines. Prime-boost immunization with heterologous microbes sharing the same CD8+ epitope can induce a large expansion of the CD8+ response; however, different vectors vary greatly in their ability to boost for reasons that are poorly understood. To investigate how efficient memory T cell expansion can occur, we evaluated immune regulatory events and Ag presentation after secondary immunization with strong and weak boosting vectors. We found that dendritic cells were essential for T cell boosting and that Ag presentation by these cells was regulated by cognate memory CD8+ T cells. When weak boosting vectors were used for secondary immunization, pre-established CD8+ T cells were able to effectively curtail Ag presentation, resulting in limited CD8+ T cell expansion. In contrast, a strong boosting vector, vaccinia virus, induced highly efficient Ag presentation that overcame regulation by cognate T cells and induced large numbers of memory CD8+ T cells to expand. Thus, efficient targeting of Ag to dendritic cells in the face of cognate immunity is an important requirement for T cell expansion.

Original languageEnglish (US)
Pages (from-to)64-71
Number of pages8
JournalJournal of Immunology
Volume180
Issue number1
StatePublished - Jan 1 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Memory CD8<sup>+</sup> T cell responses expand when antigen presentation overcomes T cell self-regulation'. Together they form a unique fingerprint.

  • Cite this

    Cockburn, I. A., Chakravarty, S., Overstreet, M. G., García-Sastre, A., & Zavala, F. (2008). Memory CD8+ T cell responses expand when antigen presentation overcomes T cell self-regulation. Journal of Immunology, 180(1), 64-71.