Petty Christopher S, Tompkins Mary B, Tompkins Wayne A
Immunology Program, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
J Acquir Immune Defic Syndr. 2008 Feb 1;47(2):148-60. doi: 10.1097/QAI.0b013e318160df70.
We have reported that CD4+CD25+ T-regulatory (Treg) cells are fully activated for suppressor function in feline immunodeficiency virus (FIV)-infected cats. Studies have suggested that surface transforming growth factor-beta (TGFbeta; membrane TGFbeta [mTGFbeta]) is a feature of activated CD4+CD25+ Treg cells and may play a role in Treg homeostasis and suppressor function. Herein, we explore the role of TGFbeta in feline Treg homeostasis and suppressor function and what effect FIV infection of cats might have on these processes. Stimulation of CD4+CD25- T helper (Th) cells with Concanavalin A (ConA) plus TGFbeta converts them to Treg-like cells capable of suppressor function. Reverse-transcription polymerase chain reaction and flow cytometry revealed that these ConA/TGFbeta-converted Treg cells upregulate Foxp3 and mTGFbeta. ConA stimulation of CD4+CD25- T cells upregulates TGFbeta receptor II (RII), and pretreatment of these cells with anti-TGFbeta-RII antibodies blocks the TGFbeta-induced conversion to Treg cells. Pretreatment of ConA/TGFbeta-converted Treg cells with anti-TGFbeta antibodies also abrogates their suppressor function, suggesting that Treg homeostasis and suppressor function may be mediated by mTGFbeta. Finally, we show that treatment of CD4+CD25+ mTGFbeta-positive Treg cells from FIV-infected cats with anti-TGFbeta antibodies or treatment of ConA-stimulated CD4+CD25- Th target cells with anti-TGFbeta-RII antibodies diminishes suppressor function. These data suggest that the recruitment of Treg cells from the Th pool and suppressor function of Treg cells are dependent on the TGFbeta/TGFbeta-RII signaling pathway and that this pathway is constitutively upregulated in asymptomatic chronically FIV-infected cats.
我们曾报道，在感染猫免疫缺陷病毒（FIV）的猫中，CD4+CD25+调节性T（Treg）细胞的抑制功能可被完全激活。研究表明，表面转化生长因子-β（TGFβ；膜TGFβ [mTGFβ]）是活化的CD4+CD25+ Treg细胞的一个特征，可能在Treg细胞稳态及抑制功能中发挥作用。在此，我们探讨TGFβ在猫Treg细胞稳态及抑制功能中的作用，以及猫感染FIV可能对这些过程产生何种影响。用伴刀豆球蛋白A（ConA）加TGFβ刺激CD4+CD25-辅助性T（Th）细胞可将其转化为具有抑制功能的类Treg细胞。逆转录聚合酶链反应和流式细胞术显示，这些经ConA/TGFβ转化的Treg细胞上调了Foxp3和mTGFβ。用ConA刺激CD4+CD25- T细胞可上调TGFβ受体II（RII），用抗TGFβ-RII抗体预处理这些细胞可阻断TGFβ诱导的向Treg细胞的转化。用抗TGFβ抗体预处理经ConA/TGFβ转化的Treg细胞也可消除其抑制功能，这表明Treg细胞稳态及抑制功能可能由mTGFβ介导。最后，我们发现，用抗TGFβ抗体处理来自感染FIV猫的CD4+CD25+ mTGFβ阳性Treg细胞，或用抗TGFβ-RII抗体处理经ConA刺激的CD4+CD25- Th靶细胞，均可削弱抑制功能。这些数据表明，从Th细胞库招募Treg细胞及Treg细胞的抑制功能依赖于TGFβ/TGFβ-RII信号通路，且该通路在无症状慢性感染FIV的猫中持续上调。
