Human Effector and Memory CD8 + T Cell Responses to Smallpox and Yellow Fever Vaccines

• Published in: Immunity (Cambridge, Mass.) Vol. 28; no. 5; pp. 710 - 722
• Main Authors: Miller, Joseph D., van der Most, Robbert G., Akondy, Rama S., Glidewell, John T., Albott, Sophia, Masopust, David, Murali-Krishna, Kaja, Mahar, Patryce L., Edupuganti, Srilatha, Lalor, Susan, Germon, Stephanie, Del Rio, Carlos, Mulligan, Mark J., Staprans, Silvija I., Altman, John D., Feinberg, Mark B., Ahmed, Rafi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2008; Elsevier Limited; Elsevier
• Subjects: B-Lymphocytes - immunology; B-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CELLIMMUNO; Histocompatibility Antigens Class I - immunology; Histocompatibility Antigens Class I - metabolism; HIV; Human immunodeficiency virus; Humans; Immunologic Memory; Infections; Life Sciences; Lymphocyte Activation; Smallpox; Smallpox Vaccine - immunology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - metabolism; Vaccination; Vaccines; Vaccinia virus - immunology; Viral infections; Yellow Fever Vaccine - immunology; Yellow Fever Vaccine - metabolism; CELLIMMUNO
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2008.02.020

To explore the human T cell response to acute viral infection, we performed a longitudinal analysis of CD8 + T cells responding to the live yellow fever virus and smallpox vaccines—two highly successful human vaccines. Our results show that both vaccines generated a brisk primary effector CD8 + T cell response of substantial magnitude that could be readily quantitated with a simple set of four phenotypic markers. Secondly, the vaccine-induced T cell response was highly specific with minimal bystander effects. Thirdly, virus-specific CD8 + T cells passed through an obligate effector phase, contracted more than 90% and gradually differentiated into long-lived memory cells. Finally, these memory cells were highly functional and underwent a memory differentiation program distinct from that described for human CD8 + T cells specific for persistent viruses. These results provide a benchmark for CD8 + T cell responses induced by two of the most effective vaccines ever developed.