Adenosine-deaminase-associated immunodeficiency. I. Differential sensitivities of lymphocyte subpopulations exposed to 2-deoxycoformycin in vivo.
Adenosine-deaminase-associated immunodeficiency. I. Differential sensitivities of lymphocyte subpopulations exposed to 2-deoxycoformycin in vivo.
复制标题
腺苷脱氨酶相关的免疫缺陷。
DOI：
10.1111/j.1365-2249.1992.tb06458.x
复制
发表时间：
1992
影响因子：
4.6
通讯作者：
Pomerantz,RJ
中科院分区：
文献类型：
--
作者：
Bagasra,O;Howeedy,A;Pomerantz,RJ
为了更好地了解腺苷脱氨酶缺失引起的免疫功能障碍的程度，我们进行了一次腹腔注射。将不同剂量的 2′-脱氧考福霉素 (2-dcf)（一种 ADA 酶的有效抑制剂）注射到成年叙利亚仓鼠体内。检查这些动物对辅助性 T 细胞依赖性 (Th-d) 和辅助性 T 细胞非依赖性 (Th-ind) 抗原产生初级体内抗体反应的能力。用 0·5 mg/kg 2-dcf 处理的仓鼠对绵羊红细胞（一种 Th-d 抗原）和 III 型肺炎球菌多糖（SIII）（一种 Th-ind 抗原）的脾斑形成细胞 (PFC) 反应增强。用 1·0 mg/kg 2-dcf 处理动物会导致 PFC 对 Th-d 抗原的反应显着降低（P < 0·001），但对 Th-ind 抗原的反应进一步增强。可能导致对这两种类型抗原的这种二分反应的一种机制是T细胞亚群的选择性功能障碍。在较高剂量（1·5–4·0 mg/kg）下，PFC 对两种类型抗原的反应均被显着抑制。低剂量 2-def 的免疫增强归因于 T 抑制细胞对 2-dcf 的敏感性增加。通过用低剂量 Th-ind 抗原启动 2-dcf 处理的动物，证实了这一假设。这些动物未能通过刺激抗原特异性抑制性 T 细胞亚群来诱导低剂量耐受。在低剂量下，发现 B 细胞和 T 辅助细胞功能完整，通过用载体匙孔血蓝蛋白 (KLH) 启动动物并用三硝基苯基-KLH 激发进一步证实了这一点。各种T细胞亚群和B细胞的这种剂量依赖性选择性敏感性可以解释在ADA缺乏严重联合免疫缺陷儿童中观察到的临床、生化和免疫学参数的异质性。
In order to obtain a better understanding of the degree of immune dysfunctions caused by the absence of adenosine deaminase, we gave a single i.p. injection of 2′‐deoxycoformycin (2‐dcf), a potent inhibitor of the enzyme ADA at various doses into adult Syrian hamsters. These animals were examined for their ability to mount primaryin vivoantibody responses to helper T cell dependent (Th‐d) and helper T cell independent (Th‐ind) antigens. Hamsters treated with 0·5 mg/kg of 2‐dcf mounted enhanced splenic plaque‐forming cell (PFC) responses to sheep erythrocytes, a Th‐d antigen, and to pneumococcal polysaccharide type III (SIII), a Th‐ind antigen. Treatment of animals with 1·0 mg/kg of 2‐dcf resulted in a significantly depressed (P< 0·001) PFC response to Th‐d antigen, but a further enhanced response to Th‐ind antigen. One mechanism which may be responsible for such a dichotomous response to these two types of antigens was selective dysfunction of T cell subpopulations. At higher doses (1·5–4·0 mg/kg), PFC responses to both types of antigens were significantly suppressed. Immunoenhancement at low doses of 2‐def was attributed to an increased susceptibility of T suppressor cells to 2‐dcf. This hypothesis was confirmed by priming the 2‐dcf‐treated animals with low‐dose Th‐ind antigens. These animals failed to induce low‐dose tolerance by stimulation of antigen‐specific suppressor T cell subsets. At low doses, B cells and T helper cell functions were found to be intact, as further confirmed by priming the animals with the carrier keyhole limpet haemocyanin (KLH) and challenging with trinitrophenyl‐KLH. This dose‐dependent selective susceptibility of various T cell subpopulations and B cells may explain the heterogeneity of clinical, biochemical and immunological parameters observed in children with ADA deficiency severe combined immunodeficiency.
登录
查看更多内容
抗干扰素毛细胞白血病脱氧考福霉素后 CD4+ 淋巴细胞的反应持续时间和恢复：7 年随访
影响因子：
11.4
作者：
J. Seymour;M. Talpaz;R. Kurzrock
通讯作者：
R. Kurzrock
喷司他丁治疗难治性淋巴瘤和皮肤 T 细胞疾病的 II 期试验。
DOI：
10.1200/jco.1991.9.4.565
发表时间：
1991
期刊：
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
影响因子：
--
作者：
Cummings,FJ;Kim,K;Neiman,RS;Comis,RL;Oken,MM;Weitzman,SA;Mann,RB;O'Connell,MJ
通讯作者：
O'Connell,MJ
影响因子：
20.3
作者：
P. Martin;G. Schoch;L. D. Fisher;Vera Byers;C. Anasetti;F. Appelbaum;Patrick G. Beatty;K. Doney;George B. McDonald;J. Sanders;K. Sullivan;R. Storb;E. Thomas;R. Witherspoon;Pavel Lomen;John Hannigan;J. Hansen
通讯作者：
P. Martin;G. Schoch;L. D. Fisher;Vera Byers;C. Anasetti;F. Appelbaum;Patrick G. Beatty;K. Doney;George B. McDonald;J. Sanders;K. Sullivan;R. Storb;E. Thomas;R. Witherspoon;Pavel Lomen;John Hannigan;J. Hansen
脱氧考福霉素治疗患者外周血中 CD4 T 细胞恢复的动力学。
DOI：
10.1093/jnci/83.22.1678
发表时间：
1991
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Steis,RG;Urba,WJ;Kopp,WC;Alvord,WG;Smith2nd,JW;Longo,DL
通讯作者：
Longo,DL
影响因子：
20.3
作者：
MARTIN, PJ;SCHOCH, G;HANSEN, JA
通讯作者：
HANSEN, JA