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Related Experiment Videos

Alloantigen-reactive Th1 development in IL-12-deficient mice

J R Piccotti1, K Li, S Y Chan

  • 1Department of Surgery, University of Michigan School of Medicine, Ann Arbor 48109, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|May 7, 1998
PubMed
Summary

Endogenous p40 subunit can promote Th1 cell development in the absence of IL-12p70, suggesting it can substitute for IL-12 in alloimmunity. Th1 development can occur independently of IL-12 and IFN-gamma, indicating alternative pathways.

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Area of Science:

  • Immunology
  • Transplantation immunology

Background:

  • Interleukin-12 (IL-12p70) is crucial for T helper 1 (Th1) cell development, primarily through inducing interferon-gamma (IFN-gamma).
  • The p40 subunit of IL-12 can form homodimers, acting as antagonists in some contexts but potentially enhancing Th1 function in others.

Purpose of the Study:

  • To investigate the role of endogenously produced p40 subunit in alloimmunity and Th1 development.
  • To determine if Th1 development can occur independently of IL-12p70 and IFN-gamma.

Main Methods:

  • Assessment of Th1 development in IL-12 p35 knockout (p35-/-) and p40 knockout (p40-/-) mice.
  • In vitro stimulation of splenocytes with Concanavalin A (Con A) or alloantigens to measure IFN-gamma production.
  • In vivo cardiac allograft transplantation in knockout mice.

Related Experiment Videos

  • Neutralization of endogenous p40 using anti-IL-12 p40 monoclonal antibody (mAb).
  • Treatment of p40-/- allograft recipients with anti-IFN-gamma mAb.

    • Main Results:

    • Splenocytes from both p35-/- and p40-/- mice produced less IFN-gamma compared to wild-type controls.
    • In vivo-sensitized Th1 cells were detected in both p35-/- and p40-/- cardiac allograft recipients.
    • Th1 development was enhanced in p35-/- recipients compared to p40-/- recipients, indicating a role for endogenous p40.
    • Neutralizing endogenous p40 in p35-/- recipients reduced Th1 development to levels seen in p40-/- mice.
    • Neutralizing IFN-gamma in p40-/- recipients did not inhibit Th1 development but led to vascular thromboses.

    Conclusions:

    • Endogenous p40 can substitute for IL-12p70 in promoting alloantigen-specific Th1 sensitization in vivo.
    • Alloreactive Th1 development can occur independently of IL-12 and IFN-gamma, suggesting the existence of alternative Th1-sensitizing pathways.