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 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.
Gauduin
Marie-Claire
MC
Division of Immunology, New England Primate Research Center, Harvard Medical School, Southborough, MA 01772, and Partners AIDS Research Center, Infectious Disease Unit, Massachusetts General Hospital, Boston 02115, USA. mcgauduin@sfbr.org
Yu
Yi
Y
Barabasz
Amy
A
Carville
Angela
A
Piatak
Mike
M
Lifson
Jeffrey D
JD
Desrosiers
Ronald C
RC
Johnson
R Paul
RP
D000818:Animals; D000918:Antibody Specificity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002908:Chronic Disease; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology*; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*