Jin F S, Youle R J, Johnson V G, Shiloach J, Fass R, Longo D L, Bridges S H
Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
J Immunol. 1991 Mar 15;146(6):1806-11.
Treatment of normal mice with a mAb to CD4 (GK1.5) was explored as a means of inhibiting the antibody response to an immunotoxin. Three days of pretreatment with 200 micrograms of GK1.5 completely abrogated the primary antibody response to a 3-micrograms dose of a mutant diphtheria toxin conjugated to an anti-transferrin receptor antibody. The same dose and schedule of anti-CD4 antibody significantly reduced and delayed, but did not prevent, the anamnestic antitoxin response in animals that had been previously primed to the immunotoxin. Three daily injections of anti-CD4 antibodies followed by weekly doses of immunotoxin resulted in a 3-wk delay in the development of antitoxin antibodies, and the kinetics of the antitoxin response correlated with the kinetics of recovery of CD4+ T cells in the spleen and lymph nodes. The antitoxin response to repeated doses of immunotoxin was completely abrogated when anti-CD4 antibodies were given every 2 wk throughout the course of immunotoxin treatment. Thus, transient depletion of Th cells during treatment can block the immune response to an immunotoxin. There was no evidence of tolerance induction with this regimen.
探索用抗CD4单克隆抗体（GK1.5）处理正常小鼠，作为抑制对免疫毒素抗体反应的一种手段。用200微克GK1.5进行三天预处理，可完全消除对3微克与抗转铁蛋白受体抗体偶联的突变白喉毒素剂量的初次抗体反应。相同剂量和方案的抗CD4抗体显著降低并延迟了，但并未阻止，先前已对免疫毒素致敏的动物的回忆性抗毒素反应。每天三次注射抗CD4抗体，随后每周注射免疫毒素剂量，导致抗毒素抗体产生延迟3周，并且抗毒素反应的动力学与脾脏和淋巴结中CD4 + T细胞恢复的动力学相关。当在整个免疫毒素治疗过程中每2周给予抗CD4抗体时，对重复剂量免疫毒素的抗毒素反应被完全消除。因此，治疗期间Th细胞的短暂耗竭可阻断对免疫毒素的免疫反应。该方案没有诱导耐受性的证据。
