Titanji Kehmia, De Milito Angelo, Cagigi Alberto, Thorstensson Rigmor, Grützmeier Sven, Atlas Ann, Hejdeman Bo, Kroon Frank P, Lopalco Lucia, Nilsson Anna, Chiodi Francesca
Microbiology and Tumor Biology Center, Karolinska Institutet, S 17177 Stockholm, Sweden.
Blood. 2006 Sep 1;108(5):1580-7. doi: 10.1182/blood-2005-11-013383. Epub 2006 Apr 27.
Circulating memory B cells are severely reduced in the peripheral blood of HIV-1-infected patients. We investigated whether dysfunctional serologic memory to non-HIV antigens is related to disease progression by evaluating the frequency of memory B cells, plasma IgG, plasma levels of antibodies to measles, and Streptococcus pneumoniae, and enumerating measles-specific antibody-secreting cells in patients with primary, chronic, and long-term nonprogressive HIV-1 infection. We also evaluated the in vitro production of IgM and IgG antibodies against measles and S pneumoniae antigens following polyclonal activation of peripheral blood mononuclear cells (PBMCs) from patients. The percentage of memory B cells correlated with CD4+ T-cell counts in patients, thus representing a marker of disease progression. While patients with primary and chronic infection had severe defects in serologic memory, long-term nonprogressors had memory B-cell frequency and levels of antigen-specific antibodies comparable with controls. We also evaluated the effect of antiretroviral therapy on these serologic memory defects and found that antiretroviral therapy did not restore serologic memory in primary or in chronic infection. We suggest that HIV infection impairs maintenance of long-term serologic immunity to HIV-1-unrelated antigens and this defect is initiated early in infection. This may have important consequences for the response of HIV-infected patients to immunizations.
在HIV-1感染患者的外周血中，循环记忆B细胞严重减少。我们通过评估记忆B细胞的频率、血浆IgG、麻疹抗体和肺炎链球菌抗体的血浆水平，并对原发性、慢性和长期非进展性HIV-1感染患者的麻疹特异性抗体分泌细胞进行计数，研究了对非HIV抗原的血清学记忆功能障碍是否与疾病进展相关。我们还评估了患者外周血单个核细胞（PBMC）多克隆激活后针对麻疹和肺炎链球菌抗原的IgM和IgG抗体的体外产生情况。记忆B细胞的百分比与患者的CD4+T细胞计数相关，因此代表了疾病进展的一个标志物。虽然原发性和慢性感染患者在血清学记忆方面存在严重缺陷，但长期非进展者的记忆B细胞频率和抗原特异性抗体水平与对照组相当。我们还评估了抗逆转录病毒疗法对这些血清学记忆缺陷的影响，发现抗逆转录病毒疗法在原发性或慢性感染中并未恢复血清学记忆。我们认为，HIV感染会损害对HIV-1无关抗原的长期血清学免疫的维持，并且这种缺陷在感染早期就已开始。这可能对HIV感染患者的免疫反应产生重要影响。
