Michaëlsson Jakob, Long Brian R, Loo Christopher P, Lanier Lewis L, Spotts Gerald, Hecht Frederick M, Nixon Douglas F
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
J Infect Dis. 2008 Jan 1;197(1):117-25. doi: 10.1086/524141.
Natural killer (NK) cells are believed to play a role in human immunodeficiency virus type 1 (HIV-1) disease progression, and NK cell levels are reduced in individuals with chronic HIV-1 infection. Interleukin (IL)-2 therapy results in an expansion of CD4(+) T cells as well as NK cells; however, little is known about the detailed effects of IL-2 therapy on NK cells in HIV-1 infection in general and in early infection in particular. Here, we investigated the effects of combined IL-2 therapy and antiretroviral therapy (ART) on the number, frequency, phenotype, and interferon (IFN)-gamma production of NK cells in individuals with early HIV-1 infection. Patients randomized to receive combined ART and IL-2 therapy predominantly expanded CD56(dim) NK cells, and the expansion was greater than in patients randomized to receive ART alone. Importantly, NK cell receptor expression and IFN-gamma production were maintained over time. This reconstitution of NK cells may be useful in helping contain viremia if patients discontinue therapy or develop drug resistance.
自然杀伤(NK)细胞被认为在1型人类免疫缺陷病毒(HIV-1)疾病进展中发挥作用,并且慢性HIV-1感染者的NK细胞水平会降低。白细胞介素(IL)-2治疗可导致CD4(+) T细胞以及NK细胞的扩增;然而,总体而言,尤其是在早期感染中,关于IL-2治疗对HIV-1感染中NK细胞的详细影响知之甚少。在此,我们研究了IL-2联合抗逆转录病毒疗法(ART)对早期HIV-1感染个体NK细胞数量、频率、表型和干扰素(IFN)-γ产生的影响。随机接受ART联合IL-2治疗的患者主要扩增了CD56(dim) NK细胞,且这种扩增大于随机仅接受ART治疗的患者。重要的是,NK细胞受体表达和IFN-γ产生随时间得以维持。如果患者停止治疗或产生耐药性,这种NK细胞的重建可能有助于控制病毒血症。