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Cell Immunol. 2011;266(2):180-6. doi: 10.1016/j.cellimm.2010.10.002. Epub 2010 Oct 30.

CD4(+) T-cells are important in regulating macrophage polarization in C57BL/6 wild-type mice.

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Center for Gene Therapeutics and Institute for Infectious Disease Research, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.


During activation, macrophages undergo physiological changes affecting their surface protein expression and cytokine production and have been subsequently categorized into M1 (classically-activated) and M2 (alternatively-activated) macrophages. It remains unclear which lymphocyte population provides the immune microenvironment to regulate macrophage polarization. In this study, we establish a functional and phenotypic profile of peritoneal macrophages from C57BL/6 wild-type mice. We also showed that Rag1(-/-) and Rag2(-/-)γc(-/-) mice have similar, exaggerated M1 characteristics in comparison to control mice, suggesting that NK and/or NK-T cells may not be essential in this process. By controlling for environmental factors, we determine that lymphocyte-derived cytokines, rather than inherent properties of macrophages themselves, are crucial for their regulation. Lastly, we report that macrophages from CD4(-/-) mice display an M1 profile, suggesting that CD4(+) T-cells play a dominant role over other lymphocyte populations in providing the cytokine environment for regulating macrophages towards an M2 profile under normal wild-type conditions.

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