Immunization with live attenuated SIV strains has proved to be one of the most effective strategies to induce protective immunity in the SIV/macaque model To better understand the role that CD4+ T helper responses may play in mediating protection in this model, we characterized SIV-specific proliferative and cytokine responses in macaques immunized with live attenuated SIV strains Macaques chronically infected with the attenuated virus SIVmac239'nef had strong proliferative responses to SIV proteins, with stimulation indices of up to 72 Limiting dilution and ELISPOT analysis revealed SIV-specific T helper precursor frequencies of up to 200 per 106 PBMC The magnitude of the proliferative response to SIV gag varied inversely with the degree of attenuation gag-specific, but not envelope-specific, responses were lower in animals infected with the more highly attenuated SIV strains SIVmac239'3 and SIVmac239'4 SIV-specific stimulation of lymphocytes from SIVmac 239 'nef-vaccinated macaques resulted in secretion of interferon-gamma, RANTES, MIP-1alpha and MIP-1beta but not IL-4 or IL-10 Intracellular flow cytometric analysis confirmed the production of IL-2, IFN-gamma, RANTES and MIP-1beta by CD4+ T cells following p55 stimulation The ability of live attenuated SIV to induce a strong, sustained type 1 T helper response may play a role in the success of this vaccination approach to generate protection against challenge with wild-type SIV Aldovini, A - Children's Hospital, Harvard Medical School Analysis of immune responses generated by DNA vaccination Bunnel, B - Ohio State University In vivo retroviral transduction of hematopoietic stem cells Crooks, G - Children's Hospital of Los Angeles In vitro T lymphopoiesis of single hematopoietic cells using rhesus thymic stromal cultures Dube', I - University of Toronto Retroviral transduction of rhesus hematopoietic stem cells using long term bone marrow cultures Feinberg, M - Office of AIDS Research, National Institutes of Health, Bethesda, MD Characterization of cell mediated immune responses in SIV infected sooty mangabeys Grant, R - University of California, San Francisco Characterization of cell mediated immune responses in SIV infected sooty mangabeys Hirsch, MS - Massachusetts General Hospital/Harvard Medical School, Boston, MA Interactions between SIV and rhesus cytomegalovirus Jordan, C - University of Kentucky Analysis of foreign gene expression in hematopoietic cells following retroviral transduction of hematopoietic stem cells Knipe, D - Harvard Medical School, Boston, MA Herpesvirus vectors as vaccines for AIDS Letvin, NL - Beth Israel Hospital/Harvard Medical School, Boston, MA Immunophenotyping of rhesus macaques Lisziewicz, J - Research Institute for Genetic and Human Therapy Gene therapy using a polymeric TAR decoy MacVitte, T - University of Maryland Analysis of foreign gene expression in hematopoietic cells following retroviral transduction of hematopoietic stem cells Malech, H - NIH, Bethesda, MD Analysis of foreign gene expression in hematopoietic cells following retroviral transduction of hematopoietic stem cells Marasco, W - Dana Farber Cancer Institute, Boston, MA Human antitat intrabody gene therapy against SHIV McClure, H - Yerkes Regional Primate Research Center/Emery University, Atlanta, GA Characterization of cell mediated immune responses in SIV-infected sooty mangabeys Morgan, R - NIH, Bethesda, MD In vivo transduction of hematopoietic stem cells Mulligan, R - Harvard Medical School, Boston, MA Identification of hematopoietic stem cells Robinson, H - University of Massachusetts Medical School, Worcester, MA Characterization of cytotoxic T lymphocyte responses induced by DNA vaccination Sachs, D - Massachusetts General Hospital/Harvard Medical School, Boston, MA Xenogeneic stem cell and thymic replacement in AIDS Scadden, D - Massachusetts General Hospital/Harvard Medical School, Boston, MA Characterization of hematopoietic stem cells in monkeys and humans Sklar, J - Brigham and Women's Hospital/Harvard Medical School, Boston, MA Analysis of the role of notch and jagged in T cell development Strayer, D - Jefferson Medical College, Philadelphia, PA Transduction of hematopoietic stem cells using SV40-based vectors Sykes, M - Massachusetts General Hospital/Harvard Medical School, Boston, MA Xenogeneic stem cell and thymic replacement in AIDS Walker, BD - Massachusetts General Hospital/Harvard Medical School, Boston, MA Immune reconstitution of HIV-infected individuals Wang, F - Brigham and Women's Hospital/Harvard Medical School, Boston, MA Infection of rhesus macaques with Epstein Barr virus Wong-Staal, F - University of California, San Diego Gene Therapy using a SIV-specific Ribozyme Zimmerberg, J - National Institutes of Health, Bethesda, MD Three dimensional analysis of thymic stromal cultures
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