人类免疫缺陷病毒感染对巨细胞病毒特异性免疫的影响:高效抗逆转录病毒治疗前后针对pp65和IE1的T细胞反应可能反映巨细胞病毒生物学特性的改变。
Influence of HIV infection on cytomegalovirus-specific immunity: T-cell responses to pp65 and IE1 before and after HAART may reflect altered cytomegalovirus biology.
作者信息
Scherrenburg Jolanda, Schellens Ingrid Mm, van Baarle Debbie
机构信息
Department of Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.
出版信息
Antivir Ther. 2011;16(4):565-75. doi: 10.3851/IMP1800.
BACKGROUND
Data are inconclusive whether treatment with HAART induces functional recovery of HIV-specific T-cells. Since the introduction of HAART, a marked decrease of cytomegalovirus (CMV) disease - for which untreated HIV-infected individuals are at increased risk - is observed, suggesting that this treatment influences CMV-specific T-cell immunity.
METHODS
To study potential functional recovery of HIV- and CMV-specific T-cells, CD4(+) and CD8(+) T-cell responses were measured longitudinally after in vitro expansion using gag, pp65 and IE1 peptide pools, during HIV infection and after long-term HAART.
RESULTS
HIV-specific T-cell function, measured by interferon (IFN)-γ production, was low after initiation of HAART. Interestingly, the cytotoxic function - measured by CD107a expression - of these T-cells temporarily increased after start of treatment, suggesting some functional recovery. The pp65-specific CD8(+) T-cell responses tended to decrease during HIV infection, whereas pp65-specific CD4(+) T-cell responses decreased upon treatment with HAART. Both pp65-specific CD4(+) and CD8(+) T-cell responses were low after initiation of HAART compared to healthy controls. By contrast, IE1-specific CD4(+) T-cell responses increased during the course of HIV infection. After initiation of HAART, IE1-specific T-cell responses decreased, but IE1-specific CD8(+) T-cells seemed increased compared to healthy controls.
CONCLUSIONS
This study suggests that HIV-infection leads to an altered CMV biology, affecting pp65- and IE1-specific T-cell responses in a different way, which is not restored by treatment with long-term HAART.
背景
关于高效抗逆转录病毒疗法(HAART)治疗是否能诱导HIV特异性T细胞功能恢复,数据尚无定论。自HAART引入以来,观察到巨细胞病毒(CMV)疾病显著减少,未接受治疗的HIV感染者患CMV疾病的风险增加,这表明该治疗会影响CMV特异性T细胞免疫。
方法
为研究HIV特异性和CMV特异性T细胞的潜在功能恢复情况,在HIV感染期间及长期HAART治疗后,使用gag、pp65和IE1肽库进行体外扩增后,纵向测量CD4(+)和CD8(+) T细胞反应。
结果
HAART开始后,通过干扰素(IFN)-γ产生测量的HIV特异性T细胞功能较低。有趣的是,这些T细胞的细胞毒性功能(通过CD107a表达测量)在治疗开始后暂时增加,表明有一定的功能恢复。在HIV感染期间,pp65特异性CD8(+) T细胞反应趋于下降,而在HAART治疗后,pp65特异性CD4(+) T细胞反应下降。与健康对照相比,HAART开始后,pp65特异性CD4(+)和CD8(+) T细胞反应均较低。相比之下,IE1特异性CD4(+) T细胞反应在HIV感染过程中增加。HAART开始后,IE1特异性T细胞反应下降,但与健康对照相比,IE1特异性CD8(+) T细胞似乎增加。
结论
本研究表明,HIV感染导致CMV生物学改变,以不同方式影响pp65和IE1特异性T细胞反应,长期HAART治疗无法恢复这种改变。