Janoff E N, Hardy W D, Smith P D, Wahl S M
Department of Medicine, Veterans Affairs Medical Center, University of Minnesota School of Medicine, Minneapolis 55417.
J Immunol. 1991 Oct 1;147(7):2130-5.
To evaluate the integrity of humoral immunologic memory among persons with HIV infection, we measured the levels, specificity, and functional affinity of circulating antibodies to vaccine-related recall Ag, tetanus (TT) and diphtheria toxoids (DT), and to naturally acquired measles virus, in sera from 17 HIV-seronegative control subjects, 17 asymptomatic HIV-seropositive patients, and 10 patients with AIDS. Preimmunization levels of TT- and measles-specific IgG were similar in all groups, although DT-specific IgG was lower in AIDS patients. Four wk after immunization with TT3 and DT, all groups showed significantly increased specific antibody levels (p less than 0.02). The asymptomatic HIV+ patients and control subjects achieved similar peak serum levels of TT-specific IgG (102 +/- 32 and 169 +/- 36 micrograms/ml, respectively). In contrast, the AIDS patients had lower peak values of both TT- and DT- specific IgG (p less than 0.05). Peak levels correlated directly with the number of CD4+ T cells (p less than 0.05). However, 80 to 100% of all participants tested, independent of HIV status, showed higher levels of TT- and DT-specific IgG 6 mo after immunization compared with preimmunization levels. The antitoxoid antibodies were specific as they did not cross-react with other Ag in competitive inhibition experiments. In addition, all groups exhibited antibodies to TT and DT both pre- and postimmunization of equivalent functional affinity (avidity) (Kd = 10(-10)-10(-11) mol/liter). We conclude that, in contrast to the profoundly depressed humoral responses to new Ag, persons with asymptomatic HIV infection retain humoral immunity to certain recall Ag. These levels of specific IgG to three recall Ag are not proportional to elevated levels of total serum IgG in HIV-infected patients. In addition, many patients with HIV respond to challenge with recall Ag by producing significant amounts of high affinity IgG that may persist over time.
为评估HIV感染者体内体液免疫记忆的完整性,我们检测了17名HIV血清阴性对照者、17名无症状HIV血清阳性患者和10名艾滋病患者血清中针对疫苗相关回忆抗原破伤风(TT)和白喉类毒素(DT)以及自然感染的麻疹病毒的循环抗体水平、特异性和功能亲和力。所有组中TT和麻疹特异性IgG的免疫前水平相似,尽管艾滋病患者中DT特异性IgG较低。用TT3和DT免疫4周后,所有组的特异性抗体水平均显著升高(p<0.02)。无症状HIV+患者和对照者的TT特异性IgG血清峰值水平相似(分别为102±32和169±36μg/ml)。相比之下,艾滋病患者的TT和DT特异性IgG峰值均较低(p<0.05)。峰值水平与CD4+T细胞数量直接相关(p<0.05)。然而,所有接受检测的参与者中,80%至100%,无论HIV状态如何,与免疫前水平相比,免疫后6个月TT和DT特异性IgG水平均更高。抗类毒素抗体具有特异性,因为它们在竞争性抑制实验中不与其他抗原发生交叉反应。此外,所有组在免疫前后针对TT和DT均表现出具有同等功能亲和力(亲和力)的抗体(解离常数Kd=10-10-10-11mol/L)。我们得出结论,与对新抗原的体液反应严重受损相反,无症状HIV感染者对某些回忆抗原有体液免疫。这些针对三种回忆抗原的特异性IgG水平与HIV感染患者血清总IgG水平升高不成比例。此外,许多HIV患者通过产生大量可能随时间持续存在的高亲和力IgG来应对回忆抗原的刺激。