Isogai Susumu, Jedrzkiewicz Sean, Taha Rame, Hamid Qutayba, Martin James G
Meakins Christie Laboratories, Department of Medicine, McGill University, Montreal, Quebec, Canada.
J Allergy Clin Immunol. 2005 Mar;115(3):521-6. doi: 10.1016/j.jaci.2004.11.036.
The role of CD8+ T cells in the immune response to airway challenge with an allergen is poorly understood.
The aim of this study was to test the hypothesis that resident naive CD8+ T cells modulate the magnitude of CD4+ T cell-dependent allergic airway responses.
Cervical lymph node CD4+ T cells (2 x 10(6)) were harvested from ovalbumin (OVA)- or sham-sensitized rats and injected intraperitoneally into naive Brown Norway recipients. The recipients were treated with a CD8alpha mAb (OX-8) to deplete the resident CD8+ T cells (n = 12) or mouse ascites (n = 12). Two days after adoptive transfer, the recipient animals were OVA challenged, lung resistance was measured for 8 hours, and bronchoalveolar lavage (BAL) was performed.
After OVA challenge, primed CD4-transferred CD8-depleted rats had larger early airway responses and late airway responses compared with primed CD4-transferred CD8-nondepleted rats (early airway responses: 158.6% +/- 19.2% vs 115.7% +/- 5.9%, P < .05; late airway responses: 8.5% +/- 1.7% vs 4.4% +/- 0.9%, P < .05). BAL eosinophilia was also greater (4.67% +/- 0.45% vs 2.34 +/- 0.26%, P < .01). The cells in BAL fluid expressing IL-4 mRNA were not significantly changed by CD8 depletion, but IL-5 mRNA+ cells were higher in number, and IFN-gamma mRNA+ cells were fewer in the CD8-depleted group.
Resident CD8+ T cells downregulate the late allergic response and airway inflammation evoked by CD4+ T-cell transfers in Brown Norway rats. This downregulation does not require antigen priming.
CD8 + T细胞在对变应原气道激发的免疫反应中的作用尚不清楚。
本研究旨在验证驻留幼稚CD8 + T细胞调节CD4 + T细胞依赖性过敏性气道反应强度这一假说。
从卵清蛋白(OVA)致敏或假致敏大鼠中收获颈淋巴结CD4 + T细胞(2×10⁶个),并腹腔注射给幼稚的棕色挪威大鼠受体。受体用CD8α单克隆抗体(OX - 8)处理以清除驻留的CD8 + T细胞(n = 12)或小鼠腹水(n = 12)。过继转移两天后,对受体动物进行OVA激发,测量8小时的肺阻力,并进行支气管肺泡灌洗(BAL)。
OVA激发后,与经CD4过继转移且未清除CD8的大鼠相比,经CD4过继转移且清除CD8的大鼠具有更大的早期气道反应和晚期气道反应(早期气道反应:158.6%±19.2%对115.7%±5.9%,P <.05;晚期气道反应:8.5%±1.7%对4.4%±0.9%,P <.05)。BAL嗜酸性粒细胞增多也更明显(4.67%±0.45%对2.34±0.26%,P <.01)。BAL液中表达IL - 4 mRNA的细胞数量在清除CD8后无显著变化,但清除CD8组中IL - 5 mRNA +细胞数量更多,IFN - γ mRNA +细胞数量更少。
在棕色挪威大鼠中,驻留CD8 + T细胞可下调由CD4 + T细胞转移诱发的晚期过敏反应和气道炎症。这种下调不需要抗原致敏。