coestímulos

Coestímulos, also known as costimulatory signals, are crucial for the complete activation of T lymphocytes. While antigen presentation by MHC molecules is the primary signal (Signal 1) for T cell activation, it is often insufficient on its own to induce a robust and sustained immune response. Coestimulatory signals, typically provided by the same antigen-presenting cell, are required as a second signal (Signal 2). This second signal helps to overcome tolerance mechanisms and promote T cell proliferation, differentiation, and survival, while also preventing anergy, a state of unresponsiveness.

A well-characterized coestimulatory pathway involves the interaction between B7 molecules (CD80 and CD86) on antigen-presenting cells and CD28 on T cells. Engagement of CD28 by B7 molecules delivers a potent coestimulatory signal that enhances T cell receptor signaling, leading to increased cytokine production and cell division. Conversely, the interaction between B7 molecules and CTLA-4 (CD152) on T cells, which is expressed later during T cell activation, serves as a negative regulator, dampening T cell responses.

Other coestimulatory molecules and pathways also exist, contributing to the fine-tuning of T cell immunity. These include the ICOS/ICOS-L pathway, which is important for T follicular helper cell differentiation, and the OX40/OX40-L and 4-1BB/4-1BBL pathways, which are involved in T cell survival and memory formation. The balance between coestimulatory and coinhibitory signals dictates the outcome of T cell activation and plays a critical role in maintaining immune homeostasis and preventing autoimmunity. Dysregulation of coestimulatory pathways can have significant implications for immune-related diseases and the development of immunotherapies.