IDENTIFICATION OF RANTES, MIP-1-ALPHA, AND MIP-1-BETA AS THE MAJOR HIV-SUPPRESSIVE FACTORS PRODUCED BY CD8(+) T-CELLS

IDENTIFICATION OF RANTES, MIP-1-ALPHA, AND MIP-1-BETA AS THE MAJOR HIV-SUPPRESSIVE FACTORS PRODUCED BY CD8(+) T-CELLS
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DOI:
10.1126/science.270.5243.1811
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发表时间:
1995-12-15
期刊:
影响因子:
56.9
通讯作者:
LUSSO, P
LUSSO, P
中科院分区:
综合性期刊1区
文献类型:
--
作者:
COCCHI, F;DEVICO, AL;LUSSO, P

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有证据表明,CD 8(+)T淋巴细胞参与体内人类免疫缺陷病毒(HIV)感染的控制,通过细胞溶解机制或释放HIV抑制因子(HIV-SF)。趋化因子RANTES、MIP-1 α和MIP-1 β被鉴定为由CD 8(+)T细胞产生的主要HIV-SF。从永生化CD 8(+)T细胞克隆的培养上清液中纯化的两种活性蛋白显示与人RANTES和MIP-1 α的序列相同。RANTES、MIP-1 α和MIP-1 β由永生化和原代CD 8(+)T细胞释放。由这些细胞产生的HIV-SF活性被针对RANTES、MIP-1 α和MIP-1 β的中和抗体的组合完全阻断。重组人RANTES、MIP-1 α和MIP-1 β诱导了对HIV-1、HIV-2和猿免疫缺陷病毒(SIV)不同毒株的剂量依赖性抑制。这些数据可能与艾滋病的预防和治疗有关。
Evidence suggests that CD8(+) T lymphocytes are involved in the control of human immunodeficiency virus (HIV) infection in vivo, either by cytolytic mechanisms or by the release of HIV-suppressive factors (HIV-SF). The chemokines RANTES, MIP-1 alpha, and MIP-1 beta were identified as the major HIV-SF produced-by CD8(+) T cells. Two active proteins purified from the culture supernatant of an immortalized CD8(+) T cell clone revealed sequence identity with human RANTES and MIP-1 alpha. RANTES, MIP-1 alpha, and MIP-1 beta were released by both immortalized and primary CD8(+) T cells. HIV-SF activity produced by these cells was completely blocked by a combination of neutralizing antibodies against RANTES, MIP-1 alpha, and MIP-1 beta. Recombinant human RANTES, MIP-1 alpha, and MIP-1 beta induced a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). These data may have relevance for the prevention and therapy of AIDS.