| RRC ID |
12700
|
| 著者 |
Yoshida A, Tanaka R, Kodama A, Yamamoto N, Ansari AA, Tanaka Y.
|
| タイトル |
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.
|
| ジャーナル |
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.
|
| 巻・号 |
12(4)
|
| ページ |
235-42
|
| 公開日 |
2005-12-1
|
| 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*
|
| リソース情報 |
| 遺伝子材料 |
pCM-hIL4 (RDB01685)
pCM-hGM (RDB01687) |
