Memory CD8+ T Cell Responses Expand When Antigen Presentation Overcomed T Cell Self-Regulation




Cockburn, Ian
Chakravarty, Sumana
Overstreet, Michael G
Garcia-Sastre, Adolfo
Zavala, Fidel

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American Association of Immunologists


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.



Keywords: adenovirus vector; antigen; malaria vaccine; seryltyrosylvalylprolylserylalanylglutamylglutaminylisoleucine; unclassified drug; virus vector; animal experiment; article; autoregulation; CD8+ T lymphocyte; cell expansion; cellular immunity; controlled stud



Journal of Immunology


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