Regulation of CD8+ T cells undergoing primary and secondary responses to infection in the same host.
Naive Ag-specific CD8(+) T cells expand, contract, and become memory cells after infection and/or vaccination. Memory CD8(+) T cells provide faster, more effective secondary responses against repeated exposure to the same pathogen. Using an adoptive transfer system with low numbers of trackable nontransgenic memory CD8(+) T cells, we showed that secondary responses can be comprised of both primary (naive) and secondary (memory) CD8(+) T cells after bacterial (Listeria monocytogenes) and/or viral (lymphocytic choriomeningitis virus) infections. The level of memory CD8(+) T cells present at the time of infection inversely correlated with the magnitude of primary CD8(+) T cell responses against the same epitope but directly correlated with the level of protection against infection. However, similar numbers of Ag-specific CD8(+) T cells were found 8 days postinfection no matter how many memory cells were present at the time of infection. Rapid contraction of primary CD8(+) T cell responses was not influenced by the presence of memory CD8(+) T cells. However, contraction of secondary CD8(+) T cell responses was markedly prolonged compared with primary responses in the same host mice. This situation occurred in response to lymphocytic choriomeningitis virus or L. monocytogenes infection and for CD8(+) T cell responses against multiple epitopes. The delayed contraction of secondary CD8(+) T cells was also observed after immunization with peptide-coated dendritic cells. Together, the results show that the level of memory CD8(+) T cells influences protective immunity and activation of naive precursors specific for the same epitope but has little impact on the magnitude or program of the CD8(+) T cell response.
Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
Vladimir P
VP
Badovinac
Kelly A Nordyke
KA
Messingham
Sara E
SE
Hamilton
John T
JT
Harty
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology / Q000637:transplantation / Q000821:virology; D002455:Cell Division / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007114:Immunization / Q000379:methods; D007117:Immunization, Secondary / Q000379:methods; D007156:Immunologic Memory; D007399:Interphase / Q000276:immunology; D008088:Listeriosis / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D009698:Nucleoproteins / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000382:microbiology / Q000821:virology
D018984:Epitopes, T-Lymphocyte; D009698:Nucleoproteins; D010446:Peptide Fragments; C094246:nucleoprotein peptide 118-126, lymphocytic choriomeningitis virus