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Interleukin 1 alpha but not transforming growth factor beta inhibits tumor antigen presentation by epidermal

S Grabbe1, S Bruvers, R D Granstein

  • 1Department of Dermatology, Harvard Medical School, Boston, Massachusetts.

The Journal of Investigative Dermatology
|January 1, 1994
PubMed

Insights

Locally produced cytokines, like interleukin-1 alpha, can regulate epidermal antigen-presenting cells and influence tumor immunity. Interleukin-1 alpha, partly via tumor necrosis factor-alpha, inhibits antigen presentation, impacting protective tumor immunity.

Area of Science:

  • Immunology
  • Dermatology
  • Oncology

Background:

  • Cutaneous Langerhans cells are key antigen-presenting cells in the epidermis.
  • Epidermal Langerhans cells can present tumor antigens but often fail to induce protective immunity.
  • The role of local cytokines in regulating epidermal antigen presentation and tumor immunity is not fully understood.

Purpose of the Study:

  • To investigate if locally produced cytokines down-regulate tumor-associated antigen and alloantigen presentation by epidermal antigen-presenting cells.
  • To determine the specific roles of interleukin-1 alpha and tumor necrosis factor-alpha in regulating epidermal antigen presentation and tumor immunity.

Main Methods:

  • Immunization of mice with granulocyte-macrophage colony-stimulating factor (GM-CSF)-exposed and tumor-pulsed epidermal cells.
  • In vitro and in vivo studies involving co-incubation of epidermal cells with various cytokines (GM-CSF, IL-1α, TNF-α, TGF-β).
  • Assessment of antigen presentation using mixed epidermal cell-lymphocyte reactions and delayed-type hypersensitivity responses.

Main Results:

  • GM-CSF and tumor antigen-pulsed epidermal cells successfully immunized naive mice against a specific tumor.
  • Interleukin-1 alpha (IL-1α) inhibited both tumor-associated antigen and alloantigen presentation by epidermal cells, an effect partially mediated by tumor necrosis factor-alpha (TNF-α).
  • IL-1α inhibited delayed-type hypersensitivity responses in tumor-immune mice, while TNF-α enhanced them, indicating differential roles in primed systems.

Conclusions:

  • Interleukin-1 alpha is a significant regulator of Langerhans cell antigen-presenting function.
  • The effects of IL-1α on epidermal antigen presentation and tumor immunity are partly mediated through the induction of TNF-α.
  • Cytokine milieu within the skin plays a crucial role in modulating immune responses to tumors.

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