Okano M, Otsuki N, Azuma M, Fujiwara T, Kariya S, Sugata Y, Higaki T, Kino K, Tanimoto Y, Okubo K, Nishizaki K
Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Clin Exp Allergy. 2008 Dec;38(12):1891-900. doi: 10.1111/j.1365-2222.2008.03116.x. Epub 2008 Oct 30.
B7/CD28 family co-signalling molecules play a key role in regulating T cell activation and tolerance. Allergen-specific immunotherapy (SIT) alters allergen-specific T cell responses. However, the effect of SIT on the expression of various co-signalling molecules has not been clarified.
We sought to determine whether SIT might affect the expression of three co-inhibitory molecules, programmed death (PD)-1, B7-H1 and B and T lymphocyte attenuator (BTLA), in Japanese cedar pollinosis (JCP).
Peripheral blood mononuclear cells (PBMCs) were isolated from JCP patients who had or had not received SIT. PBMC were cultured in the presence or absence of Cry j 1, after which the cell surface expression of PD-1, B7-H1 and BTLA, as well as IL-5 production, were determined. In addition, the effect of BTLA cross-linking on IL-5 production was examined.
After Cry j 1 stimulation, no significant differences in PD-1 and B7-H1 expression were observed between SIT-treated and SIT-untreated patients. BTLA expression was down-regulated in untreated patients after Cry j 1 stimulation and up-regulated in SIT-treated patients. Up-regulation of BTLA in SIT-treated patients was particularly apparent in a CD4(+) T cell subset. IL-5 production was clearly reduced among SIT-treated patients, and the observed changes in BTLA expression correlated negatively with IL-5 production. Moreover, immobilization of BTLA suppressed IL-5 production in JCP patients.
These results suggest that both IL-5 production and down-regulation of BTLA in response to allergen are inhibited in SIT-treated patients with JCP. BTLA-mediated co-inhibition of IL-5 production may contribute to the regulation of allergen-specific T cell responses in patients receiving immunotherapy.
B7/CD28家族共信号分子在调节T细胞活化和耐受中起关键作用。变应原特异性免疫疗法（SIT）可改变变应原特异性T细胞反应。然而，SIT对各种共信号分子表达的影响尚未阐明。
我们试图确定SIT是否会影响日本雪松花粉症（JCP）患者体内三种共抑制分子程序性死亡（PD）-1、B7-H1和B及T淋巴细胞衰减器（BTLA）的表达。
从接受或未接受SIT的JCP患者中分离外周血单个核细胞（PBMC）。PBMC在有或无Cry j 1的情况下培养，之后测定PD-1、B7-H1和BTLA的细胞表面表达以及IL-5的产生。此外，检测BTLA交联对IL-5产生量的影响。
Cry j 1刺激后，接受SIT治疗和未接受SIT治疗的患者之间，PD-1和B7-H1表达无显著差异。未接受治疗的患者在Cry j 1刺激后BTLA表达下调，而接受SIT治疗的患者BTLA表达上调。接受SIT治疗患者中BTLA的上调在CD4(+) T细胞亚群中尤为明显。接受SIT治疗的患者中IL-5的产生明显减少，观察到的BTLA表达变化与IL-5产生呈负相关。此外，BTLA的固定抑制了JCP患者IL-5的产生。
这些结果表明，在接受SIT治疗的JCP患者中，变应原诱导的IL-5产生和BTLA下调均受到抑制。BTLA介导的对IL-5产生的共抑制可能有助于接受免疫治疗患者中变应原特异性T细胞反应的调节。
