Identification of a factor produced by anti-HIV CD4+ T cells induced by dendritic cell-based immunization in the hu-PBL-SCID mice

hu-PBL-SCID 小鼠树突状细胞免疫诱导的抗 HIV CD4 T 细胞产生的因子的鉴定

• 批准号: 16017288
• 负责人: TANAKA Yuetsu
• 金额: $ 9.6万
• 依托单位: University of the Ryukyus
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16017288/
• 关键词: HIV; AIDS; Dendritic cells; hu-PBL-SCID; Defense against Infectionn; 樹上細胞; CD4+T細胞; 未知因子; SCIDマウス

We have previously reported that immunization of the severe combined immunodifficiency (SCID) mice reconstituted with human peripheral blood mononuclear cells (PBMC) (hu-PBL-SCID mice) with inactivated human immunodeficiency virus type-1-pulsed (HIV-1)-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-1 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 mg/ml of a panel of HIV-1 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-g. 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)-g 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.

我们以前曾报道，用灭活的人类免疫缺陷病毒1型(HIV-1)冲击的自体树突状细胞(HIV-DC)免疫由人外周血单个核细胞(PBMC)重建的严重联合免疫缺陷(SCID)小鼠(Hu-PBL-SCID小鼠)，可以诱导出HIV-1反应的CD4^+T细胞，在体外产生一种尚未定义的新型可溶性因子，具有抗CCR5趋向性(R5)HIV-1感染的特性。这些发现使我们进行了一些研究，旨在确定在体内合成这种因子的细胞的谱系，并确定对诱导这种抗病毒因子具有特异性的HIV-1蛋白表位。我们的研究结果表明，这一特性是CD4^+T细胞的功能，而不是CD8^+T细胞的功能。从HIV-DC免疫的Hu-PBL-SCID小鼠中回收人CD_4~+T细胞，以自体贴壁PBMC为抗原提呈细胞(APC)，在含有IL-2的培养液中冲击灭活HIV-1，体外再刺激2天，以扩增HIV-1反应性CD_4~+T细胞。然后将这些重新刺激的等量CD4^+T细胞与类似的APC共培养2天，这些APC之前用10 mg/ml的一组HIV-1多肽冲击，并检测其培养上清液中R5 HIV-1抑制因子和干扰素-g的产生。本文提供的数据表明，HIV-1免疫的CD4^+T细胞产生R5抑制因子，对HIV-1 Gag、env、pol1、nef或vif多肽的反应取决于CD4^+T细胞的供体。在某些情况下观察到同时产生人干扰素-g。这些结果表明，HIV-1初始献血者PBMC中的人CD4~+T细胞具有多种HIV-1表位特异性的CD_4~+T细胞前体，能够在DC基础上接种完整灭活的HIV-1后产生R5 HIV-1抑制因子。

项目成果

Identification

• DOI: 10.1007/978-1-4419-5906-5_77
• 发表时间: 2010-09
• 期刊: Composites Part B: Engineering
• 作者: Carlisle M. Adams

Cross-linking cell surface chemokine receptors leads to isolation, activation and differentiation of monocytes into potent DC's.

交联细胞表面趋化因子受体导致单核细胞分离、激活和分化为强效 DC。

• 发表时间: 2006
• 期刊: Exp. Biol. Med. 231(4)
• 作者: Nimura F.;Zhang L.;Okuma K.;Tanaka R.;Sunakawa H.;Yamamoto N.;Tanaka Y.
• 通讯作者: Tanaka Y.

Exp Biol Med (Maywood) 231(4) : 431-43, 2006. Yamamoto N, Tanaka Y.

Exp Biol Med (Maywood) 231(4) : 431-43, 2006. Yamamoto N, Tanaka Y.

• 发表时间: 2006
• 期刊: Exp Biol Med (Maywood) 231(4)
• 作者: Nimura F;Zhang LF;Okuma K;Tanaka R;Sunakawa H
• 通讯作者: Sunakawa H

Identification of HIV-1 epitopes that induce the synthesis of a R5 HIV-1 suppressor factor by human CD4+T cells isolated from HIV-1 immunized hu-PBL SCID mice.

鉴定可诱导从 HIV-1 免疫的 hu-PBL SCID 小鼠中分离的人 CD4 T 细胞合成 R5 HIV-1 抑制因子的 HIV-1 表位。

• 发表时间: 2005
• 期刊: Clinical and Developmental Immunology 12(4)
• 作者: Yoshida A.;Kodama A.;Tanaka R.;Yamamoto N.;Ansari A.;Tanaka Y.
• 通讯作者: Tanaka Y.