Allostimulatory activity as a criterion of the functional phenotype of human macrophages

The functional phenotype of macrophages (Mφ) is determined by both differentiation factors and polarization stimuli. In mouse Mφ could be easily divided into the distinct Mφ subtypes. However, the identification of human M1 and M2 cells is much more difficult due to the lack of M1- or M2-specific markers. We assumed that the Mφ capacity to induce T cell proliferation in mixed leukocyte culture, or allostimulatory activity, may be a marker of Mφ functional phenotype. We compared the allostimulatory activity of Mφ differentiated with GM-CSF or M-CSF and polarized into M1, M2a, M2c subtypes using appropriate stimuli. GM-CSF-differentiated M1 Mφ showed pronounced allostimulatory activity whereas the polarization into M2a and M2c of GM-CSF-differentiated Mφ was associated with decreased allostimulatory activity. M-CSF-differentiated M1 Mφ demonstrated the moderate increasing of allostimulatory activity but its level has never reached that of GM-CSF-activated M1. The level of allostimulatory activity of M2a and M2c M-CSF-induced Mφ was comparable to that of GM-CSF-induced M2a and M2c Mφ. Thus, low allostimulatory activity is a common property of human M2a and M2c macrophages regardless of the differentiating factor and a polarizing stimulus and can be used to distinguish between M1 and M2 phenotypes.