Effects of subcutaneous interleukin-2 therapy on CD4 subsets and in vitro cytokine production in HIV plus subjects
Effects of subcutaneous interleukin-2 therapy on CD4 subsets and in vitro cytokine production in HIV plus subjects
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DOI：
10.1172/jci119819
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发表时间：
1997-12-01
影响因子：
15.9
通讯作者：
Tirelli, U
中科院分区：
文献类型：
--
作者：
De Paoli, P;Zanussi, S;Tirelli, U
HIV感染的特征在于CD 4+、CD 45 RA+、CD 26+和CD 28+淋巴细胞亚群的减少以及IL-2、IL-4和干扰素-γ的体外产生的减少;相反，趋化因子的产生通常增加。抗逆转录病毒化疗只能部分恢复这些异常。已提出用白细胞介素-2治疗以恢复免疫系统的功能，但IL-2发挥其活性的机制尚不清楚。本研究的目的是确定rIL-2给药对CD 4+、CD 45 RA+、CD 45 R 0+和CD 26+淋巴细胞以及对IL-2、IL-4、IL-10、IFN-γ、RANTES、10例CD 4细胞计数在200 - 500 cells/mm（3）之间的HIV+患者接受了6个周期的皮下重组IL-10治疗。2次给药，与齐多夫定和去羟肌苷联合。这种治疗方案导致了CD 4+细胞数量的显著增加和病毒血症水平的长期降低。CD 45 R 01细胞在第一个治疗周期中扩增，而CD 45 RA +/CD 26+细胞在第三个治疗周期后占主导地位。此时，IL-2、IL-4、IFN-γ和sCD 30的体外产生显著上调。这些结果表明，HIV+患者中的rIL-2诱导CD 4/CD 45 RA淋巴细胞亚型的重建。该扩增的细胞群恢复了体外产生IL-2、IL-4和IFN-γ的能力。这些作用可能通过改善他们对微生物或疫苗的免疫反应而对HIVS患者有益。
HIV infection is characterized by the reduction of the CD4+, CD45RA+, CD26+, and CD28+ lymphocyte subsets and of the in vitro production of IL-2, IL-4, and interferon-gamma; on the contrary, chemokine production is usually increased. These abnormalities are only partially restored by antiretroviral chemotherapy. Therapy with interleukin-2 has been proposed to restore the functions of the immune system, but the mechanisms by which IL-2 exerts its activities are unknown. The aim of this study was to define the effects of rIL-2 administration on CD4+, CD45RA+, CD45R0+, and CD26+ lymphocytes and on the in vitro production of IL-2, IL-4, IL-10, IFN-gamma, RANTES, and sCD30 in HIV+ patients.10 HIV+ patients with CD4 cell counts between 200 and 500 cells/mm(3) were treated with six cycles of subcutaneous recombinant IL-2 administration, in combination with zidovudine and didanosine. This therapeutic regimen resulted in a remarkable increase in the number of CD4+ cells and in the prolonged reduction of the levels of viremia. CD45R01 cells were expanded during the first cycle of therapy, while CD45RA+/CD26+ cells predominated after the third cycle. At this time, the in vitro production of IL-2, IL-4, IFN-gamma, and sCD30 were significantly upregulated.These results demonstrate that rIL-2 in HIV+ patients induces the reconstitution of the CD4/CD45RA lymphocytes subtype. This expanded cell population recovered the ability to produce in vitro IL-2, IL-4, and IFN-gamma. These effects may be beneficial to HIVS patients by improving their immune response to microorganisms or vaccines.