Proposed Model of Differential Hemin-Induced, HO-1–dependent, CD16+ Monocyte-Mediated T-cell Polarization that Might Govern Risk of Alloimmunization in Transfused Patients With SCD. In addition to its HO-1 dependent effects on CD4+ T cell subset polarization (detailed in the narrative), hemin treatment reduces IL-12 activity in stimulated monocytes from non-immunized SCD patients (left panel) but not in stimulated monocytes from alloimmunized SCD patient (right panel). As IL-12 contributes to the proinflammatory polarization state (low Treg/high Th1[Teff]) in SCD (right panel), this antagonistic effect on IL-12 activity further supports the hemin-induced anti-inflammatory polarization state (high Treg/low Th1) (left panel).Reprinted by permission from The Journal of Immunology. 2014, vol. 193, pp. 102-110. Copyright 2014. The American Association of Immunologists, Inc.