Effector T Cell Functions in Peripheral Tissues

When helper T cells arrive in peripheral tissues, they interact with various cell types, including antigen-presenting cells (APCs) such as macrophages, dendritic cells, and B cells, as well as other effector cells like neutrophils and tissue-resident cells. The interactions between T cells and APCs, particularly macrophages, play crucial roles in regulating immune responses in the peripheral tissues.

The cell-cell interactions between T cells and macrophages in peripheral tissues involve several steps:

1. Antigen Recognition: T cells recognize antigens presented by macrophages via major histocompatibility complex (MHC) molecules. This interaction occurs when T cell receptors (TCRs) on the surface of T cells recognize specific antigen peptides bound to MHC molecules on the surface of macrophages.
2. Costimulation: Costimulatory molecules, such as CD80 (B7.1) and CD86 (B7.2) on the surface of macrophages, interact with CD28 on T cells. This interaction provides the second signal necessary for T cell activation and proliferation.
3. Cytokine Production: Upon activation, helper T cells produce various cytokines depending on their subset, such as interleukins (IL-2, IL-4, IL-17), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α). These cytokines can modulate the function of macrophages, influencing their polarization into different phenotypes (e.g., M1 or M2 macrophages) and regulating their effector functions.
4. Feedback Regulation: T cells can also express molecules such as cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death-1 (PD-1), which interact with their ligands on macrophages (CD80/CD86 and PD-L1/PD-L2, respectively), providing negative feedback to regulate T cell activation and prevent excessive immune responses.

The cytokines produced by helper T cells can profoundly alter the immunological microenvironment in peripheral tissues by:

• Inducing recruitment and activation of other immune cells, such as neutrophils and eosinophils, to the site of inflammation.
• Modulating the phenotype and function of resident immune cells, such as macrophages and dendritic cells, to enhance antigen presentation, phagocytosis, and cytokine production.
• Stimulating tissue repair and remodeling processes by promoting fibroblast activation and extracellular matrix deposition.
• Regulating the balance between pro-inflammatory and anti-inflammatory responses, contributing to the resolution of inflammation and tissue homeostasis.

Overall, the interactions between helper T cells and antigen-presenting cells, particularly macrophages, orchestrate the immune response in peripheral tissues, leading to the clearance of pathogens, tissue repair, and maintenance of immune homeostasis.

Next Topic: Mixed Messages from Signal 2: Activating and Suppressive Costimulatory Molecules

Source: ChatGPT response prompted and edited by Joel Graff.

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