2025年諾貝爾生理學或醫學獎揭曉後，全球科學界再次將焦點放在日本免疫學家坂口志文（Shimon Sakaguchi）教授身上。他被譽為「免疫學界的革命者」，因為他發現並闡明免疫系統中關鍵的一項防禦機制——調節性T細胞（Regulatory T cells, 簡稱Treg），也被稱為人體的「免疫刹車系統」。這一發現徹底改變人類對免疫反應的理解，為自體免疫疾病、癌症與器官移植的治療開啟了全新方向。

坂口志文教授早在1980年代便開始研究免疫系統中那些「抑制免疫反應」的細胞。當時，主流學界普遍認為免疫系統的功能是「越強越好」，因為強大的免疫反應能殺死細菌與病毒。然而，坂口發現有一部分T細胞的行為與眾不同——它們不但不攻擊外來病原，反而會抑制免疫系統過度活化，防止人體自身組織被誤傷。這一發現最初引來不少質疑，甚至被認為與免疫學的基本原則相悖。但坂口憑藉嚴謹的實驗數據，最終證明這些細胞的存在。

1995年，坂口志文在《Journal of Immunology》發表具有里程碑意義的論文，首次明確指出這些細胞是一種具有CD4與CD25分子標誌的T細胞群體，並將其命名為「調節性T細胞（Treg）」。後來，科學界進一步確認，Treg細胞的關鍵轉錄因子為FOXP3基因。若該基因失常或缺失，免疫系統便會失控，導致嚴重的自體免疫疾病，例如第一型糖尿病、紅斑性狼瘡、克隆氏症等。這說明Treg細胞的主要任務，是像汽車的煞車系統一樣，在免疫系統過於亢奮時踩下「剎車」，讓免疫反應保持在恰當的平衡狀態。

坂口的研究揭示一個極為關鍵的概念：免疫並非越強越好，而是必須平衡。免疫系統中的「油門」與「剎車」相互制衡，缺一不可。油門由效應性T細胞（Effector T cells）負責，它們攻擊感染細胞或癌細胞；剎車則由Treg細胞負責，防止這種攻擊失控。當Treg功能過強時，可能導致癌細胞逃避免疫攻擊；當Treg功能過弱時，則可能引發自體免疫疾病。

坂口教授的發現不僅在理論上改變免疫學，更在臨床醫學上產生深遠影響。如今，許多針對癌症的免疫治療（例如PD-1、CTLA-4免疫檢查點抑制劑）都與坂口的「免疫剎車理論」有直接關聯。這些療法的原理，是暫時解除Treg或其他抑制機制的限制，讓免疫系統重新「踩油門」，攻擊腫瘤細胞。另一方面，對於像多發性硬化症、紅斑性狼瘡等自體免疫疾病，科學家則嘗試增強Treg的活性，以重建免疫耐受，使免疫系統停止攻擊自身組織。

坂口志文現為大阪大學免疫學教授，也是京都大學iPS細胞研究所的重要合作學者。他的研究被認為是近代免疫學三大基石之一，與免疫檢查點的發現、mRNA疫苗技術齊名。由於Treg的概念為全球醫學研究帶來數十年的啟發與應用，他被譽為「改寫免疫學命運的人」。

總結來說，坂口教授發現的「免疫剎車系統」不僅讓人類更深入理解自身的防禦機制，也開啟了新時代的精準醫療之路。從控制過敏、治療自體免疫病，到強化抗癌免疫反應，Treg的研究正成為連接「免疫平衡」與「生命延續」的關鍵橋樑。

The Nobel Prize–winning “immune brake system” refers to a groundbreaking discovery in immunology led by Professor Shimon Sakaguchi of Japan, who identified a special class of immune cells known as regulatory T cells (Tregs). His research fundamentally changed how scientists understand the immune system’s balance between defense and tolerance.

In a healthy immune system, T cells attack foreign invaders such as viruses and bacteria. However, if this activity goes unchecked, the body can mistakenly target its own tissues, leading to autoimmune diseases like rheumatoid arthritis, lupus, or type 1 diabetes. Sakaguchi discovered that not all T cells are attackers — a small subset, the regulatory T cells, serve as a kind of “immune brake.” These cells act as moderators that suppress excessive immune reactions, preventing the body from turning its defenses against itself.

Sakaguchi’s breakthrough dates back to the early 1990s, when he identified a molecule called CD25 that is highly expressed on regulatory T cells. He later found that another molecule, FOXP3, serves as the “master switch” gene controlling the development and function of these regulatory T cells. Mice lacking FOXP3 develop severe autoimmune disorders, showing how crucial this mechanism is for maintaining immune balance.

This “immune brake system” discovery not only deepened our understanding of autoimmune diseases but also opened new paths in cancer immunotherapy. In cancers, tumors sometimes exploit regulatory T cells to suppress the immune response, allowing cancer cells to hide from immune attack. By understanding and modulating this “immune brake,” scientists have been able to design new treatments that either enhance or release this suppression — for example, combining immune checkpoint inhibitors (like PD-1 or CTLA-4 blockers) with therapies targeting Tregs to improve anti-tumor immunity.

Sakaguchi’s work therefore stands as a cornerstone in modern immunology. It provides a theoretical and practical foundation for treating diseases on both extremes of immune dysfunction — from overactivation (autoimmunity) to suppression (cancer). The concept of the “immune brake system” redefined the immune system as not merely an attack mechanism, but a dynamic balance that must be finely tuned to preserve health.