T cell responses are a cornerstone of the immune system’s ability to defend against pathogens. These responses are initiated when T cell receptors (TCRs) recognize peptide-MHC complexes on the surface of antigen-presenting cells (APCs). However, antigen recognition alone is not sufficient to activate T cells effectively. A second signal, provided by costimulators expressed on APCs, is essential for a robust immune response.
The most well-known costimulators belong to the B7 family of molecules, which bind to receptors from the CD28 family on T cells. The interaction between B7 and CD28 is crucial for the full activation of T cells. Notably, the expression of B7 costimulators on APCs increases upon encountering microbes, which serves as a mechanism for generating optimal responses to infectious pathogens.
Interestingly, the CD28 family also includes inhibitory receptors that can suppress T cell responses. The balance between activating and inhibitory signals from this family ultimately determines the outcome of T cell activation. This balance is vital because it ensures that the immune response is neither too weak to fight infection nor too strong, which could lead to autoimmunity.
Upon activation, T cells undergo several key changes that define their response to antigen and costimulation. These changes include the upregulation of surface molecules, cytokine production, cellular proliferation, and differentiation into effector and memory cells. Some of the surface molecules induced during T cell activation are involved in the retention of T cells within lymphoid organs, migration to sites of infection, and the regulation of T cell functions.
One of the most critical cytokines produced shortly after activation is interleukin-2 (IL-2). T cells produce IL-2 and express high levels of its receptor (IL-2R), which in turn promotes their proliferation. This expansion allows for the creation of a large number of antigen-specific clones, bolstering the immune response.
The maintenance of memory T cells relies on cytokines such as IL-7, which helps prevent apoptosis and promotes the expression of survival proteins. Memory T cells are not homogenous; they represent a diverse group with distinct migration properties and functional characteristics. This diversity allows memory T cells to mount a more effective response upon encountering pathogens in the future.
As the immune system clears the antigen, it returns to a state of rest. This process is accompanied by the decline of T cell responses, primarily because the signals for continued activation are no longer present. The removal of these signals ensures that the immune system does not remain chronically activated. This is important to prevent harmful inflammation or autoimmunity.
In conclusion, T cells finely tune their responses through antigen recognition, costimulation, and cytokine signaling. This process leads to the differentiation of T cells into effector and memory cells. The interplay between activating and inhibitory signals is essential for enabling the immune system to respond effectively to infections. It also plays a crucial role in maintaining self-tolerance. Understanding these processes is crucial for developing therapies to modulate immune responses. Such therapies have potential applications in a variety of diseases, including infections, autoimmune disorders, and cancer.