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Transcriptional profiles of sorted CD8+ and CD4+ memory T cells from CP and NP and unvaccinated control RM 7 days prior to, and 4 and 14 days after wt SIVmac239 challenge by microarray analysis.

ABSTRACT: Live-attenuated SIV vaccines (LAVs) remain the most efficacious of all vaccines in nonhuman primate models of HIV/AIDS, yet the basis of their robust protection remains poorly understood. Here, we demonstrate that the degree of LAV-mediated protection against intravenous (IV) wildtype (wt) SIVmac239 challenge strongly correlates with the magnitude and function of SIV-specific, effector-differentiated T cells in lymph node (LN), but not with such T cell responses in blood or with other cellular, humoral and innate immune parameters. Maintenance of protective T cell responses was associated with persistent LAV replication in LN, which occurred almost exclusively in follicular helper T cells. Thus, effective LAVs maintain lymphoid tissue-based, effector-differentiated, SIV-specific T cells that intercept and suppress early wt SIV amplification and, if present in sufficient frequencies, can completely control and perhaps clear infection -- an observation that provides rationale for development of safe, persistent vectors that can elicit and maintain such responses.

ORGANISM(S): Homo sapiens Macaca mulatta

PROVIDER: GSE39968 | GEO | 2012/08/09

SECONDARY ACCESSION(S): PRJNA172176

REPOSITORIES: GEO

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Transcriptional profiles of sorted CD8+ and CD4+ memory T cells from CP and NP and unvaccinated control RM 7 days prior to, and 4 and 14 days after wt SIVmac239 challenge by microarray analysis.

Project description:Live-attenuated SIV vaccines (LAVs) remain the most efficacious of all vaccines in nonhuman primate models of HIV/AIDS, yet the basis of their robust protection remains poorly understood. Here, we demonstrate that the degree of LAV-mediated protection against intravenous (IV) wildtype (wt) SIVmac239 challenge strongly correlates with the magnitude and function of SIV-specific, effector-differentiated T cells in lymph node (LN), but not with such T cell responses in blood or with other cellular, humoral and innate immune parameters. Maintenance of protective T cell responses was associated with persistent LAV replication in LN, which occurred almost exclusively in follicular helper T cells. Thus, effective LAVs maintain lymphoid tissue-based, effector-differentiated, SIV-specific T cells that intercept and suppress early wt SIV amplification and, if present in sufficient frequencies, can completely control and perhaps clear infection -- an observation that provides rationale for development of safe, persistent vectors that can elicit and maintain such responses. There are two protection outcome groups, complete protect (CP) and non-protect (NP) animals. Memory T cells (CD4+ or CD8+) were sorted for three time points, seven days pre-challenge, four days post-challenge and fourteen days post-challenge.

2012-08-08 | E-GEOD-39968 | biostudies-arrayexpress

Transcriptional profiles of unfractionated lymph nodes cells obtained from completely protected, non protected and unvaccinated control rhesus macaques seven days prior to, and four and fourteen days after wt SIVmac239 challenge by microarray analysis.

2012-08-09 | GSE39967 | GEO

Project description:Live-attenuated SIV vaccines (LAVs) remain the most efficacious of all vaccines in nonhuman primate models of HIV/AIDS, yet the basis of their robust protection remains poorly understood. Here, we demonstrate that the degree of LAV-mediated protection against intravenous (IV) wildtype (wt) SIVmac239 challenge strongly correlates with the magnitude and function of SIV-specific, effector-differentiated T cells in lymph node (LN), but not with such T cell responses in blood or with other cellular, humoral and innate immune parameters. Maintenance of protective T cell responses was associated with persistent LAV replication in LN, which occurred almost exclusively in follicular helper T cells. Thus, effective LAVs maintain lymphoid tissue-based, effector-differentiated, SIV-specific T cells that intercept and suppress early wt SIV amplification and, if present in sufficient frequencies, can completely control and perhaps clear infection -- an observation that provides rationale for development of safe, persistent vectors that can elicit and maintain such responses. There are four protection outcome groups: unvaccinated control (C), complete protect (CP), non-protect (NP) and partial protect (PP). Respectively for these groups, there are 7, 9, 6 and 4 animals sampled seven days pre-challenge (minus7PCD); 9, 13, 5 and 5 animals sampled four days post-challenge (4PCD) and 8, 11, 5 and 3 fourteen days post-challenge (14PCD).

2012-08-08 | E-GEOD-39967 | biostudies-arrayexpress

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Interleukin-10 regulates reservoir establishment and persistence in antiretroviral therapy-treated, SIV-infected macaques

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