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.

我们以前曾报道用人外周血单个核细胞（PBMC）重建的重症联合免疫缺陷（SCID）小鼠免疫，（hu-PBL-SCID小鼠）与灭活的人类免疫缺陷病毒1型（HIV-1）致敏的自体树突状细胞（HIV-DC）一起刺激HIV-1反应性CD 4 ^+ T细胞，后者在体外产生一种尚未确定的新型可溶性因子，抗CCR 5嗜性（R5）HIV-1感染的病毒特性。这些发现使我们进行了旨在鉴定体内合成这种因子的细胞谱系的研究，并确定了对诱导这种抗病毒因子具有特异性的HIV-1蛋白的表位。我们的研究结果表明，这种特性是CD 4 ^+ T细胞的功能，而不是CD 8 ^+ T细胞的功能。因此，从HIV-DC免疫的hu-PBL-SCID小鼠中回收人CD 4 ^+ T细胞，并通过与自体贴壁PBMC共培养2天进行体外再刺激，所述自体贴壁PBMC作为抗原呈递细胞（APC），所述抗原呈递细胞（APC）预先在含IL-2的培养基中用灭活的HIV-1进行脉冲，以扩增HIV-1反应性CD 4 ^+ T细胞。然后将这些再刺激的CD 4 ^+ T细胞的等分试样与类似的APC共培养2天，这些APC先前用10 mg/ml的一组HIV-1肽脉冲，并检测其培养上清液中R5 HIV-1抑制因子和IFN-g的产生。本文提供的数据表明，HIV-1致敏的CD 4 ^+ T细胞产生R5抑制因子，以响应多种HIV-1 gag、env、pol、nef或vif肽，这取决于CD 4 ^+ T细胞的供体。同时生产的人干扰素（IFN）-g观察到在某些情况下。这些结果表明，HIV-1初治供体PBMC中的人CD 4 ^+ T细胞具有多种HIV-1表位特异性CD 4 ^+ T细胞前体，这些前体能够在DC基础上接种完整灭活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.