Hertl Michael, Veldman Christian
Department of Dermatology, University of Erlangen-Nürnberg, Hartmannstr. 14, D-91054 Erlangen, Germany.
Autoimmun Rev. 2003 Sep;2(5):278-83. doi: 10.1016/s1568-9972(03)00035-1.
Pemphigus encompasses a group of life-threatening blistering diseases of the skin in which loss of adhesion between keratinocytes is caused by autoantibodies (Ab) against desmogleins (Dsg) 1 and 3. There is major interest in characterizing autoreactive T cells that are presumably critical for the induction and regulation of Ab production. In a recent study, peripheral Dsg3-reactive T helper (Th) cells from patients with acute onset, chronic active and remittent pemphigus vulgaris (PV) were quantitated by MACS secretion assay. Dsg3-reactive Th2 cells were detected at similar frequencies in all the studied PV patients while the number of autoreactive Th1 cells exceeded those of the Th2 cells in chronic active PV. Noteworthy, healthy carriers of the PV-associated HLA class II alleles, DRbeta10402 and DQbeta10503, exhibited exclusively Th1 reactivity against Dsg3. The titers of Dsg3-reactive IgG were directly related to the ratio of autoreactive Th1/Th2 cells. Moreover, T cell recognition of Dsg3 was restricted by these HLA class II alleles. These findings strongly suggest that (1) Dsg3-reactive Th2 cells are restricted to PV, (2) distinct HLA class II alleles are critical for T cell recognition of Dsg3, and (3) Ab production is associated with both, Th1 and Th2 cells.
天疱疮是一组危及生命的皮肤水疱性疾病，其中角质形成细胞之间的黏附丧失是由针对桥粒芯糖蛋白（Dsg）1和3的自身抗体（Ab）引起的。人们对鉴定自身反应性T细胞非常感兴趣，这些T细胞可能对抗体产生的诱导和调节至关重要。在最近的一项研究中，通过MACS分泌测定法对急性发作、慢性活动性和缓解期寻常型天疱疮（PV）患者外周血中Dsg3反应性辅助性T（Th）细胞进行了定量分析。在所有研究的PV患者中，检测到Dsg3反应性Th2细胞的频率相似，而在慢性活动性PV中，自身反应性Th1细胞的数量超过了Th2细胞。值得注意的是，携带PV相关HLA-II类等位基因DRβ10402和DQβ10503的健康携带者仅表现出针对Dsg3的Th1反应性。Dsg3反应性IgG的滴度与自身反应性Th1/Th2细胞的比例直接相关。此外，T细胞对Dsg3的识别受这些HLA-II类等位基因的限制。这些发现强烈表明：（1）Dsg3反应性Th2细胞仅限于PV；（2）不同的HLA-II类等位基因对T细胞识别Dsg3至关重要；（3）抗体产生与Th1和Th2细胞均有关。
