Tight regulation of memory CD8(+) T cells limits their effectiveness during sustained high viral load

To design successful vaccines for chronic diseases, an understanding of memory CD8(+) T cell responses to persistent antigen restimulation is critical. However, most studies comparing memory and naive cell responses have been performed only in rapidly cleared acute infections. Herein, by comparing t...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Vol. 35; no. 2; p. 285
Main Authors: West, Erin E, Youngblood, Ben, Tan, Wendy G, Jin, Hyun-Tak, Araki, Koichi, Alexe, Gabriela, Konieczny, Bogumila T, Calpe, Silvia, Freeman, Gordon J, Terhorst, Cox, Haining, W Nicholas, Ahmed, Rafi
Format: Journal Article
Language:English
Published: United States 26.08.2011
Subjects:
Acute Disease
Adoptive Transfer
Animals
Antigens, CD - immunology
Antigens, CD - metabolism
Arenaviridae Infections - immunology
Arenaviridae Infections - virology
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - metabolism
CD8-Positive T-Lymphocytes - pathology
CD8-Positive T-Lymphocytes - virology
Cell Proliferation
Cells, Cultured
Chronic Disease
Cytokines - immunology
Cytokines - metabolism
Immunologic Memory
Lymphocytic choriomeningitis virus - pathogenicity
Lymphocytic choriomeningitis virus - physiology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Paracrine Communication
Receptors, Antigen, T-Cell, alpha-beta - genetics
Receptors, Immunologic - immunology
Receptors, Immunologic - metabolism
Signaling Lymphocytic Activation Molecule Family
T-Lymphocyte Subsets - immunology
T-Lymphocyte Subsets - metabolism
T-Lymphocyte Subsets - pathology
T-Lymphocyte Subsets - virology
Viral Load
Viral Vaccines
ISSN:1097-4180, 1097-4180
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Summary:To design successful vaccines for chronic diseases, an understanding of memory CD8(+) T cell responses to persistent antigen restimulation is critical. However, most studies comparing memory and naive cell responses have been performed only in rapidly cleared acute infections. Herein, by comparing the responses of memory and naive CD8(+) T cells to acute and chronic lymphocytic choriomeningitis virus infection, we show that memory cells dominated over naive cells and were protective when present in sufficient numbers to quickly reduce infection. In contrast, when infection was not rapidly reduced, because of high antigen load or persistence, memory cells were quickly lost, unlike naive cells. This loss of memory cells was due to a block in sustaining cell proliferation, selective regulation by the inhibitory receptor 2B4, and increased reliance on CD4(+) T cell help. Thus, emphasizing the importance of designing vaccines that elicit effective CD4(+) T cell help and rapidly control infection.
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ISSN:1097-4180
1097-4180
DOI:10.1016/j.immuni.2011.05.017