Adaptive immune cells temper initial innate responses.

Area of Science:

• Immunology
• Innate Immunity
• Adaptive Immunity

Background:

• Toll-like receptors (TLRs) mediate innate immune responses to pathogens.
• Adaptive immunity, particularly T cells, is crucial for clearing infections.
• The role of T cells in modulating early innate responses is not fully understood.

Purpose of the Study:

• To investigate the role of T cells in regulating innate immune responses and preventing fatal inflammation.
• To determine if the absence of T cells exacerbates innate immune responses.

Main Methods:

• Utilized lymphocyte-deficient mice (T-cell deficient or Rag-1 deficient) and wild-type mice.
• Administered viral infection or poly(I:C) to induce TLR3 activation.
• Depleted CD4+ and CD8+ T cells in wild-type mice.
• Transferred T lymphocytes into Rag-1-deficient mice.
• Assessed cytokine storm, NK cell activity, and tumor necrosis factor production.

Main Results:

• Lymphocyte-deficient mice exhibited fatal cytokine storms upon viral infection or poly(I:C) administration, dependent on NK cells and TNF.
• T cells (both CD4+ and CD8+) were necessary and sufficient to temper the early innate immune response.
• Antigen-independent suppression of cytokine surges was observed through direct contact between T cells and innate immune cells.

Conclusions:

• Adaptive immune cells, particularly T cells, play an unexpected and critical role in tempering excessive innate immune responses.
• The absence of T cells can lead to life-threatening cytokine storms driven by innate immunity.
• T cells provide a regulatory brake on innate immunity, preventing hyperinflammation.