DIMINUTION OF INDUCIBLE LYMPHOKINE-ACTIVATED KILLER-CELL ACTIVITY IN INDIVIDUALS WITH AIDS-RELATED DISORDERS

DIMINUTION OF INDUCIBLE LYMPHOKINE-ACTIVATED KILLER-CELL ACTIVITY IN INDIVIDUALS WITH AIDS-RELATED DISORDERS
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DOI:
10.1097/00002030-199012000-00004
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发表时间:
1990-12-01
期刊:
影响因子:
3.8
通讯作者:
BRENNER, B
BRENNER, B
中科院分区:
医学2区
文献类型:
--
作者:
GRYLLIS, C;WAINBERG, MA;BRENNER, B

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我们比较了来自HIV血清阳性者、AIDS受试者和健康对照者外周血的淋巴因子激活的杀伤(LAK)细胞裂解一组自然杀伤(NK)敏感和NK耐药肿瘤和病毒感染靶点的相对能力。我们已经发现,与来自健康对照的类似衍生细胞相比,来自HIV血清阳性群体的LAK细胞显示出显著的(尽管降低的)裂解U937、K562和RAJI靶细胞系的能力。在HIV血清阳性无症状人群和AIDS人群中LAK活性的降低反映了单个LAK细胞的细胞毒性潜能的显著降低。对照组、无症状血清学阳性组和AIDS组的最大LAK细胞毒性潜能相当。来自HIV血清阳性人群的LAK细胞显示出相对于其未感染的对应物增强的裂解HIV感染的U937靶标的能力。HIV感染的U937与U937细胞溶解的这些增强是由于最大细胞介导的细胞溶解平台的增加。在LAK细胞产生之前,从外周血中消耗NK(CD56+)淋巴细胞显著降低随后的特异性和总的诱导性LAK活性。在一些受试者中,LAK细胞产生之前的外周血T细胞耗竭导致LAK细胞随后富集溶细胞活性,而在其他受试者中,类似的T细胞耗竭损害诱导型LAK细胞应答。
We have compared the relative ability of lymphokine-activated killer (LAK) cells derived from peripheral blood of HIV-seropositive people, AIDS subjects, and healthy controls, to lyse a panel of natural killer (NK)-sensitive and NK-resistant tumor and virally-infected targets. We have found that LAK cells derived from HIV-seropositive populations show a significant, albeit reduced, capacity to lyse U937, K562, and RAJI target cell lines, in comparison with similarly derived cells from healthy controls. The reductions in LAK activity in both HIV-seropositive asymptomatic and AIDS populations reflect a significant reduction in cytotoxic potential of individual LAK cells. The maximal LAK cytotoxic potentials of control, asymptomatic seropositive, and AIDS populations are comparable. LAK cells derived from HIV-seropositive populations show an enhanced capacity to lyse HIV-infected U937 targets relative to their uninfected counterparts. These enhancements in HIV-infected U937 versus U937 cytolysis arise from increases in the maximal cell-mediated cytolytic plateau. Depletion of NK (CD56+) lymphocytes from peripheral blood prior to LAK cell generation markedly diminishes subsequent specific and total inducible LAK activity. In some subjects, peripheral blood T-cell depletion prior to LAK cell generation results in LAK cells that are subsequently enriched for cytolytic activity, whereas in other subjects similar T-cell depletion impairs inducible LAK cell responses.