CELLULAR IMMUNE FUNCTION IN AIDS AND CANCER
CELLULAR IMMUNE FUNCTION IN AIDS AND CANCER
批准号:
6100958
负责人:
G M SHEARER
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
关键词:
AIDS AIDS vaccines HIV infections Wiskott Aldrich syndrome cellular immunity cytokine disease /disorder proneness /risk helper T lymphocyte human subject humoral immunity immunogenetics influenza vaccines longitudinal human study pediatric AIDS prognosis serotyping tissue /cell culture virus DNA virus antigen virus load
中文摘要
HIV感染导致免疫调节细胞因子变化,
降低增强细胞免疫(CI)的1型细胞因子,
2型细胞因子增加,增强体液免疫(HI)。IL-12和
IL-10分别增强CI和HI,并且由
单核细胞/巨噬细胞(M/M)是HIV感染的重要靶标。M/M
从HIV+患者中产生的IL-12水平降低,
IL-10的表达,与体外感染HIV的M/M一样。IL-12 p40和p35 mRNA
在晚期患者中表达降低,但在无症状患者中不降低。
HIV蛋白酶治疗儿童艾滋病的临床研究
抑制剂表明,
负荷和增加的CD 4计数没有表现出正常化的IL-12和IL-12。
10生产这一发现表明,蛋白酶诱导的
CD 4计数和病毒载量的变化并不反映在改善免疫
功能感染艾滋病毒的母亲未感染的新生儿的M/M不
产生IL-12,与未感染HIV的新生儿M/M相比,
产生IL-12的母亲。HIV诱导的细胞因子失调可能
可能是由于信号转导和激活剂的减少,
转录(STAT),如来自HIV感染患者的T细胞以及
在体外用HIV-1感染的T细胞表现出STAT 5水平降低,
而不是其他已知的STAT。血清阴性,艾滋病毒暴露,T细胞-
反应性个体表现出显性1型细胞因子谱,
用HIV抗原刺激,而HIV感染者显示
占主导地位的2型细胞因子模式。源自HLA的CD 8 + T细胞系
同种抗原混合淋巴细胞刺激产生一种因子,
PHA刺激的自体和同种异体靶标的HIV感染,以及
还抑制CMV感染人成纤维细胞系。这
同种异体抗原刺激的CD 8抗病毒因子似乎没有任何
B-趋化因子。该因子抑制T-嗜性、M-嗜性和
HIV-1的原代分离株,以及慢性感染的细胞系。
因此,这种同种异体刺激因子能够在体外阻断
多种HIV分离株,以及一种机会性病毒,
在艾滋病中是个问题。AZT被掺入胎儿脐带血中
大多数在怀孕期间接受AZT的妇女的白细胞。
根据小鼠模型的经验,这一发现提高了
AZT诱导的子代长期致癌的可能性。
艾滋病标题:艾滋病毒/艾滋病的免疫缺陷。
英文摘要
Immunoregulatory cytokine changes result from HIV infection, with
decreased type 1 cytokines that enhance cellular immunity (CI) and
increased type 2 cytokines that augment humoral immunity (HI). IL-12 and
IL-10 enhance CI and HI, respectively, and are produced by
monocytes/macrophages (M/M), important targets of HIV infection. M/M
from HIV+ patients produced reduced levels of IL-12 and increased levels
of IL-10, as did M/M infected in vitro with HIV. IL-12 p40 and p35 mRNA
expression was reduced in advanced but not in asymptomatic patients.
Therapeutic trials of pediatric AIDS patients with HIV protease
inhibitors suggested that patients who presented with reduced viral
loads and increased CD4 counts did not exhibit normalized IL-12 and IL-
10 production. This finding suggests that protease inhibitor-induced
changes in CD4 count and viral load is not reflected in improved immune
function. M/M from uninfected newborns of HIV-infected mothers do not
produce IL-12, in contrast to the M/M of newborns of HIV uninfected
mothers that do produce IL-12. HIV-induced cytokine dysregulation may
be due to a reduction in signal transducers and activators of
transcription (STATs), as T cells from HIV-infected patients as well as
T cells infected in vitro with HIV-1 exhibited reduced levels of STAT5,
but not of the other known STATs. Seronegative, HIV-exposed, T cell-
responsive individuals exhibited a dominant type 1 cytokine profile when
stimulated with HIV antigens, whereas HIV-infected individuals showed
a dominant type 2 cytokine pattern. CD8+ T cell lines resulting from HLA
alloantigen mixed lymphocyte stimulation generated a factor that blocked
HIV infection of PHA stimulated autologous and allogeneic targets, and
also inhibited CMV infection of human fibroblast cell lines. This
alloantigen stimulated CD8 anti-viral factor does not appear to be any
of the b-chemokines. The factor inhibited T-tropic, M-tropic, and
primary isolates of HIV-1, as well as a chronically- infected cell line.
Thus, this allo-stimulated factor is capable in vitro of blocking
multiple HIV isolates, as well as one of the opportunistic viruses that
is problematic in AIDS. AZT was incorporated into the fetal cord blood
leukocytes from a majority of women who received AZT during pregnancy.
Based on experience from a murine model, this finding raises the
possibility of long-term AZT-induced carcinogenesis in the offspring.
AIDS title: Immune Defects in HIV/AIDS.
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批准号:4691755
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项目类别:
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资助金额:$0.0万
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批准号:2463771
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资助金额:$0.0万
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资助金额:$0.0万
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批准号:3813474
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依托单位:
海外基金