Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Laboratory of High Complexity, Fernandes Figueira National Institute for The Health of Mother, Child, and Adolescent, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Front Immunol. 2024 Apr 16;15:1379376. doi: 10.3389/fimmu.2024.1379376. eCollection 2024.
The immune system is traditionally classified as a defense system that can discriminate between self and non-self or dangerous and non-dangerous situations, unleashing a tolerogenic reaction or immune response. These activities are mainly coordinated by the interaction between innate and adaptive cells that act together to eliminate harmful stimuli and keep tissue healthy. However, healthy tissue is not always the end point of an immune response. Much evidence has been accumulated over the years, showing that the immune system has complex, diversified, and integrated functions that converge to maintaining tissue homeostasis, even in the absence of aggression, interacting with the tissue cells and allowing the functional maintenance of that tissue. One of the main cells known for their function in helping the immune response through the production of cytokines is CD4 T lymphocytes. The cytokines produced by the different subtypes act not only on immune cells but also on tissue cells. Considering that tissues have specific mediators in their architecture, it is plausible that the presence and frequency of CD4 T lymphocytes of specific subtypes (Th1, Th2, Th17, and others) maintain tissue homeostasis. In situations where homeostasis is disrupted, such as infections, allergies, inflammatory processes, and cancer, local CD4 T lymphocytes respond to this disruption and, as in the healthy tissue, towards the equilibrium of tissue dynamics. CD4 T lymphocytes can be manipulated by tumor cells to promote tumor development and metastasis, making them a prognostic factor in various types of cancer. Therefore, understanding the function of tissue-specific CD4 T lymphocytes is essential in developing new strategies for treating tissue-specific diseases, as occurs in cancer. In this context, this article reviews the evidence for this hypothesis regarding the phenotypes and functions of CD4 T lymphocytes and compares their contribution to maintaining tissue homeostasis in different organs in a steady state and during tumor progression.
免疫系统传统上被分类为一种防御系统，可以区分自我和非自我，或危险和非危险的情况，引发耐受反应或免疫反应。这些活动主要由先天和适应性细胞的相互作用协调，这些细胞共同作用以消除有害刺激并保持组织健康。然而，健康的组织并不总是免疫反应的终点。多年来，积累了大量证据，表明免疫系统具有复杂、多样化和整合的功能，这些功能汇聚在一起以维持组织内稳态，即使在没有攻击的情况下，与组织细胞相互作用并允许该组织的功能维持。已知有助于通过细胞因子产生帮助免疫反应的主要细胞之一是 CD4 T 淋巴细胞。不同亚型产生的细胞因子不仅作用于免疫细胞，而且作用于组织细胞。考虑到组织在其结构中有特定的介质，因此可以合理地认为，特定亚型（Th1、Th2、Th17 等）的 CD4 T 淋巴细胞的存在和频率维持组织内稳态。在稳态被破坏的情况下，如感染、过敏、炎症过程和癌症，局部 CD4 T 淋巴细胞对这种破坏做出反应，就像在健康组织中一样，朝着组织动力学的平衡方向发展。肿瘤细胞可以操纵 CD4 T 淋巴细胞来促进肿瘤的发展和转移，使其成为各种类型癌症的预后因素。因此，了解组织特异性 CD4 T 淋巴细胞的功能对于开发针对组织特异性疾病的新策略至关重要，就像在癌症中一样。在这种情况下，本文综述了关于 CD4 T 淋巴细胞表型和功能的这一假设的证据，并比较了它们在稳态和肿瘤进展过程中对维持不同器官组织内稳态的贡献。
