Association of cytokine polymorphic inheritance and in vitro cytokine production in anti-CD3/CD28-stimulated peripheral blood lymphocytes

Transplantation. 2001 Oct 27;72(8):1444-50. doi: 10.1097/00007890-200110270-00019.


Background: Genetic variations in cytokine genes are thought to regulate cytokine protein production. However, studies using T cell mitogens have not always demonstrated a significant relationship between cytokine polymorphisms and in vitro protein production. Furthermore, the functional consequence of a polymorphism at position -330 in the IL-2 gene has not been described. We associated in vitro protein production with cytokine gene polymorphic genotypes after costimulation of cultured peripheral blood lymphocytes.

Methods: PBL were isolated from forty healthy volunteers. Cytokine protein production was assessed by enzyme-linked immunosorbent assay. Polymorphisms in interleukin- (IL) 2, IL-6, IL-10, tumor necrosis factor (TNF-alpha), tumor growth factor (TGF-beta), and interferon (IFN-gamma) were determined by polymerase chain reaction (PCR).

Results: Statistical difference between protein production and cytokine polymorphic variants in the IL-10, IFN-gamma, and TNF-alpha genes was not evident after 48-hour stimulation with concanavalin-A. In contrast, after anti-CD3/CD28 stimulation significant differences (P<0.05) were found among high and low producers for IL-2, IL-6, and among high, intermediate, and low producers for IFN-gamma, and IL-10. Augmented levels of IL-2 in individuals that were homozygous for the polymorphic IL-2 allele were due to an early and sustained enhancement of IL-2 production. No association was found among TNF-alpha and TGF-beta genotypes and protein production.

Conclusion: Polymorphisms in IL-2, IL-6, IL-10, and IFN-gamma genes are associated with their protein production after anti-CD3/CD28 stimulation. The profound effect of the IL-2 gene polymorphism in homozygous individuals may serve as a marker for those that could mount the most vigorous allo- or autoimmune responses, or perhaps become tolerant more easily.

MeSH terms

  • CD28 Antigens / immunology*
  • CD3 Complex / immunology*
  • Concanavalin A / pharmacology
  • Cytokines / biosynthesis*
  • Cytokines / genetics*
  • Genotype
  • Humans
  • Interferon-gamma / biosynthesis
  • Interleukin-10 / biosynthesis
  • Interleukin-2 / biosynthesis
  • Interleukin-6 / biosynthesis
  • Lymphocytes / metabolism*
  • Polymorphism, Genetic*
  • Tumor Necrosis Factor-alpha / biosynthesis


  • CD28 Antigens
  • CD3 Complex
  • Cytokines
  • Interleukin-2
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Concanavalin A
  • Interleukin-10
  • Interferon-gamma