Immune system cytokines

Interleukins: IL-7 and IL-15

These cytokines play a critical role in maintaining lymphocyte populations.

Interleukin-7 (IL-7) is the main factor in T-cell homeostasis and development. It is spontaneously secreted by bone marrow stroma, thymic epithelium, and keratinocytes. Its synthesis is tightly regulated: only IFNγ is able to significantly enhance its production.

The IL-7 receptor consists of α and γ(c) subunits associated with intracellular kinases Jak1 and Jak3. The signal is transmitted via STAT1 and STAT5 factors. The main result of IL-7 action is the production of the Bcl-2 protein, which protects cells from apoptosis. Without this cytokine, human T-lymphopoiesis halts at the double-negative thymocyte stage (DN2). For mature T cells, IL-7 serves as a proliferation cofactor and a stimulator of other cytokine secretion.

Interleukin-15 (IL-15) is structurally similar to IL-2 (mass 14 kDa). Its receptor is notable for sharing two out of three chains with the IL-2 receptor, while the third (α) is strictly specific. IL-15 is produced by monocytes, macrophages, and epithelium. Its functions largely resemble the effects of IL-2: it stimulates the division of T and B lymphocytes, NK cells, and also maintains the survival of epithelium and CD8+ memory T cells. IL-15 deficiency leads to a drop in the levels of intraepithelial T cells and NKT lymphocytes.

BAFF and APRIL Factors

Both proteins belong to the tumor necrosis factor (TNF) superfamily and exist in both membrane-bound and soluble forms due to alternative splicing. Their main target is B lymphocytes.

These cytokines protect cells from death (also via Bcl-2 induction) and stimulate their activation. There are three types of receptors that perceive their signals:

• BAFF-R — binds primarily BAFF, necessary for B-cell maturation.
• BCMA — prefers APRIL, responsible for the survival of plasma cells in the bone marrow.
• TACI — binds both factors equally well, regulates T-independent responses.

The balance of these molecules is extremely critical: their excess triggers autoimmune reactions and lymphoproliferative disorders, while their deficiency causes common variable immunodeficiency.

Thymic Microenvironment

The thymus provides a complex environment for T-cell maturation, where different populations secrete their own set of regulators.

• Thymic epithelial cells (TECs) secrete numerous cytokines (IL-1, IL-6, IL-7, SCF, TGFβ) and chemokines (SDF-1, TECK). Cortical TECs produce a narrower spectrum of substances compared to subcapsular and medullary TECs.
• Stromal and antigen-presenting cells (fibroblasts, dendritic, and myoid cells) complement this cocktail by releasing growth factors (FGF, PDGF, M-CSF) and specific chemokines.
• Thymocytes themselves actively participate in cytokine metabolism at various stages of development. For example, mature helpers (CD4⁺CD8⁻) secrete a vast spectrum of interleukins (IL-2, IL-3, IL-4, IL-5, IL-10, IL-13) and tumor necrosis factors.

Additionally, the thymic epithelium produces peptide factors: neurotransmitters (oxytocin, vasopressin, somatostatin) and specific thymic hormones (thymosins, thymulin, thymopoietins).

Class and exam questions

What else to study on this topic

• Detailed mechanism of intracellular signal transduction via Jak/STAT
• Thymocyte development stages (double-negative, double-positive, single-positive) and their markers
• The role of chemokines (SDF-1, TECK) in cell migration within the thymus
• Differences between membrane-bound and soluble cytokine forms
• Mechanisms of action of thymic hormones (thymosin, thymulin) at the systemic level

Other topics in the "Adaptive Immunity" section

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.