Induction of a virus-specific effector-memory CD4+ T cell response by attenuated SIV infection

We investigated simian immunodeficiency virus (SIV)-specific CD4+ T cell responses in rhesus macaques chronically infected with attenuated or pathogenic SIV strains. Analysis of SIVDeltanef-infected animals revealed a relatively high frequency of SIV-specific CD4+ T cells representing 4-10% of all C...

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Published in:The Journal of experimental medicine 2006-11, Vol.203 (12), p.2661-2672
Main Authors: Gauduin, Marie-Claire, Yu, Yi, Barabasz, Amy, Carville, Angela, Piatak, Mike, Lifson, Jeffrey D, Desrosiers, Ronald C, Johnson, R Paul
Format: Article
Language:English
Subjects:
Animals
Antibody Specificity
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - virology
Chronic Disease
Immunologic Memory - immunology
Immunophenotyping
Lymphocyte Activation - immunology
Macaca mulatta
Simian Acquired Immunodeficiency Syndrome - immunology
Simian Acquired Immunodeficiency Syndrome - virology
Simian Immunodeficiency Virus - immunology
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Summary:We investigated simian immunodeficiency virus (SIV)-specific CD4+ T cell responses in rhesus macaques chronically infected with attenuated or pathogenic SIV strains. Analysis of SIVDeltanef-infected animals revealed a relatively high frequency of SIV-specific CD4+ T cells representing 4-10% of all CD4+ T lymphocytes directed against multiple SIV proteins. Gag-specific CD4+ T cells in wild-type SIV-infected animals were 5-10-fold lower in frequency and inversely correlated with the level of plasma viremia. SIV-specific CD4+ cells from SIVDeltanef animals were predominantly CD27-CD28-CD45RAlowCCR7-CCR5-, consistent with an effector-memory subset, and included a fully differentiated CD45RA+CCR7- subpopulation. In contrast, SIV-specific CD4+ T cells from SIV-infected animals were mostly CD27+CD28+CD45RA-CCR7+CCR5+, consistent with an early central memory phenotype. The CD45RA+CCR7-CD4+ subset from SIVDeltanef animals was highly enriched for effector CD4+ T cells, as indicated by the perforin expression and up-regulation of the lysosomal membrane protein CD107a after SIV Gag stimulation. SIV-specific CD4+ T cells in attenuated SIV-infected animals were increased in frequency in bronchioalveolar lavage and decreased in lymph nodes, consistent with an effector-memory T cell population. The ability of SIVDeltanef to induce a high frequency virus-specific CD4+ T cell response with direct effector function may play a key role in protective immunity produced by vaccination with attenuated SIV strains.
ISSN:0022-1007
1540-9538
DOI:10.1084/jem.20060134