RRC ID 12700
Author Yoshida A, Tanaka R, Kodama A, Yamamoto N, Ansari AA, Tanaka Y.
Title Identification of HIV-1 epitopes that induce the synthesis of a R5 HIV-1 suppression factor by human CD4+ T cells isolated from HIV-1 immunized hu-PBL SCID mice.
Journal Clin. Dev. Immunol.
Abstract We have previously reported that immunization of the severe combined immunodeficiency (SCID) mice reconstituted with human peripheral blood mononuclear cells (PBMC) (hu-PBL-SCID mice) with inactivated human immunodeficiency virus type-1 (HIV-1)-pulsed-autologous dendritic cells (HIV-DC) elicits HIV-1-reactive CD4(+) T cells that produce an as yet to be defined novel soluble factor in vitro with anti-viral properties against CCR5 tropic (R5) HIV-1 infection. These findings led us to perform studies designed to identify the lineage of the cell that synthesizes such a factor in vivo and define the epitopes of HIV-1 protein that have specificity for the induction of such anti-viral factor. Results of our studies show that this property is a function of CD4(+) but not CD8(+) T cells. Human CD4(+) T cells were thus recovered from the HIV-DC-immunized hu-PBL-SCID mice and were re-stimulated in vitro by co-culture for 2 days with autologous adherent PBMC as antigen presenting cells, APC previously pulsed with inactivated HIV in IL-2-containing medium to expand HIV-1-reactive CD4(+) T cells. Aliquots of these re-stimulated CD4(+) T cells were then co-cultured with similar APC's that were previously pulsed with 10 microg/ml of a panel of HIV peptides for an additional 2 days, and their culture supernatants were examined for the production of both the R5 HIV-1 suppression factor and IFN-gamma. The data presented herein show that the HIV-1 primed CD4(+) T cells produced the R5 suppression factor in response to a wide variety of HIV-1 gag, env, pol, nef or vif peptides, depending on the donor of the CD4(+) T cells. Simultaneous production of human interferon (IFN)-gamma was observed in some cases. These results indicate that human CD4(+) T cells in PBMC of HIV-1 naive donors have a wide variety of HIV-1 epitope-specific CD4(+) T cell precursors that are capable of producing the R5 HIV-1 suppression factor upon DC-based vaccination with whole inactivated HIV-1.
Volume 12(4)
Pages 235-42
Published 2005-12
DOI 10.1080/17402520500391557
PII VT682625431R5212
PMID 16584108
PMC PMC2270741
MeSH Animals Antiviral Agents / metabolism* Antiviral Agents / pharmacology CD4-Positive T-Lymphocytes / immunology* CD4-Positive T-Lymphocytes / metabolism CD4-Positive T-Lymphocytes / virology* CD8-Positive T-Lymphocytes / immunology CD8-Positive T-Lymphocytes / virology Cells, Cultured Dendritic Cells / immunology Dendritic Cells / virology Epitopes / immunology* Growth Inhibitors / biosynthesis Growth Inhibitors / isolation & purification* Growth Inhibitors / physiology HIV-1 / growth & development* HIV-1 / immunology* Humans Leukocytes, Mononuclear / immunology Leukocytes, Mononuclear / virology Mice Mice, Inbred BALB C Mice, Knockout Mice, SCID Virus Inactivation*
DNA material pCM-hIL4 (RDB01685) pCM-hGM (RDB01687)