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Immune responses in 4-1BB (CD137)-deficient mice
Byoung S Kwon1, Jose C Hurtado, Zang H Lee
1Immunomodulation Research Center, University of Ulsan, Ulsan, Korea. bskwon@uou.ulsan.ac.kr
Journal of Immunology (Baltimore, Md. : 1950)
|May 23, 2002
Summary
Mice lacking the 4-1BB receptor showed altered immune responses, with enhanced T cell proliferation but diminished overall T cell function and increased myeloid progenitor cells. This suggests 4-1BB is crucial for regulating T cell immunity and myeloid cell development.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- 4-1BB (CD137) is a TNFR superfamily member and an inducible costimulatory molecule on T cells.
- It regulates T cell responses independently of CD28 stimulation.
- In vitro, 4-1BB expression is induced by T cell activation stimuli.
Purpose of the Study:
- To investigate the physiological role of 4-1BB in adaptive immunity.
- To characterize the immune system of mice genetically deficient in the 4-1BB receptor.
Main Methods:
- Generation and analysis of 4-1BB-deficient mice.
- Assessment of humoral immune responses to viral and protein antigens.
- Evaluation of T cell proliferation, cytokine production, and CTL activity in vitro.
- Analysis of myeloid progenitor cell populations in mutant mice.
Main Results:
- 4-1BB-deficient mice were viable and fertile with normal development.
- Humoral responses to vesicular stomatitis virus were comparable to wild-type mice.
- IgG2a and IgG3 responses to keyhole limpet hemocyanin were reduced in mutant mice.
- T cells from deficient mice showed enhanced proliferation but diminished cytokine production and CTL activity.
- 4-1BB deficiency led to an increase in myeloid progenitor cells in peripheral blood, bone marrow, and spleen.
Conclusions:
- 4-1BB plays a critical role in regulating T cell-mediated immunity, impacting both proliferation and effector functions.
- The absence of 4-1BB influences humoral immune responses, particularly IgG subclass production.
- 4-1BB signaling is involved in the regulation of myeloid progenitor cell growth and homeostasis.