T lymphocytes

Main T lymphocyte subpopulations

"Classical" αβ T cells make up the overwhelming majority (85–90%) and circulate in the bloodstream, settling in secondary lymphoid organs (primarily in the T zones of lymph nodes and spleen). They are divided into two main fractions depending on coreceptors and their assigned tasks:

• CD4+ T lymphocytes (T helper cells). They recognize antigenic peptides in complex with MHC class II molecules. Their main task is to provide auxiliary signals for the activation of macrophages and B lymphocytes. Contact of these cells with dendritic cells triggers a T-dependent immune response.
• CD8+ T lymphocytes (cytotoxic T lymphocytes, CTLs, T killer cells). They recognize the antigen presented by MHC class I molecules. They perform the function of destroying cells carrying a foreign or altered antigen.

In addition, there is a separate developmental branch — γδ T cells (10–15%). They have a limited receptor diversity (TCR), do not require antigen presentation via MHC molecules, and are localized mainly in mucous membranes (barrier tissues).

Natural regulatory T cells (Treg)

This is a specific, antigen-independent subpopulation originating from CD4+ cells.

Their main function is the prevention of autoaggression. They control and suppress the activity of autospecific T lymphocyte clones that mistakenly escaped deletion in the thymus and entered the periphery, and can also limit any other forms of immune response.

Key markers of such cells include the intracellular factor FOXP3, and on the membrane — CD25 molecules (at high density) and CTLA-4 (CD152).

Development and markers

The maturation process of T lymphocytes takes place in the unique microenvironment of thymic epithelial cells. Differentiation takes longer than that of B lymphocytes because it requires fine-tuning of the antigen-recognizing apparatus — the T-cell receptor (TCR).

Important molecules are present on the surface of mature T cells:

• The TCR–CD3 complex. At the same time, there are 10 times more CD3 molecules on the membrane than the TCRs themselves.
• Coreceptors CD4 or CD8, which determine the direction of the cell's function.
• The costimulatory molecule CD28.

Naive cells that have not yet encountered "their" antigen are characterized by the expression of molecules that help them migrate: L-selectin (CD62L) and the chemokine receptor CCR7, as well as integrins (LFA-1, VLA-4). The survival of these cells heavily depends on interleukin-7 (IL-7) and basic signals from the TCR.

Lymphocyte recirculation

T lymphocytes are constantly in motion, patrolling the body. Their route is as follows: lymphoid organ $\rightarrow$ lymph $\rightarrow$ bloodstream $\rightarrow$ postcapillary venules $\rightarrow$ return to the lymphoid organ.

The strict direction of this movement is ensured by the interaction of chemokine receptors and adhesion molecules on the cell surface with corresponding structures in the tissues. This guarantees that T cells get precisely to the areas of lymphoid organs where they are needed. After contacting an antigen, some cells are diffusely distributed in non-lymphoid barrier-type tissues (skin, mucous membranes).

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Dynamics of TCR V-gene rearrangement and expression of TdT, RAG, and Notch genes.
• Stages of thymocyte differentiation: from double-negative (DN1–DN4) to double-positive (DP).
• Features of the receptor apparatus of γδ T cells and their localization.
• Structure and cellular composition of primary and secondary lymphoid organs.
• The role of macrophages in the first line of immune defense and secretion of pro-inflammatory cytokines.

Other topics in the section "Introduction to Immunology"

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