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Alemtuzumab mediates the CD39 + T‐regulatory cell response via CD23 + macrophages
Author(s) -
Remez Lital,
GanelinCohen Esther,
Safina Dina,
Hellmann Mark A,
Lotan Itay,
Bosak Noam,
Buxbaum Chen,
Vaknin Adi,
Shifrin Alla,
Rozenberg Ayal
Publication year - 2021
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1111/imcb.12431
Subject(s) - foxp3 , peripheral blood mononuclear cell , immunology , population , il 2 receptor , cd14 , monocyte , cd38 , cd23 , cytotoxic t cell , interleukin 7 receptor , biology , t cell , medicine , flow cytometry , antibody , immune system , microbiology and biotechnology , cd34 , in vitro , immunoglobulin e , stem cell , biochemistry , environmental health
Alemtuzumab (ALM) effectively prevents relapses of multiple sclerosis (MS). It causes lymphocyte depletion with subsequent enhancement of the T‐regulatory cell population. Direct administration of ALM to T cells causes cytolysis. However, the T cells may be indirectly affected by monocyte‐derived cells, which are resistant to ALM cytotoxicity. We aimed to examine whether ALM modulates monocytes and whether the crosstalk between monocytes and lymphocytes previously exposed to ALM would result in anti‐inflammatory effects. The CD14 + monocytes of 10 healthy controls and 10 MS (treatment naive) patients were isolated from peripheral blood mononuclear cells (PBMCs), exposed to ALM and reintroduced to PBMCs depleted of CD14 + cells. The macrophage profile was assessed and T‐cell markers were measured. ALM promoted M2 anti‐inflammatory phenotype as noted by an increased percentage in the populations of CD23 + , CD83 + and CD163 + cells. The CD23 + cells were the most upregulated (7‐fold, P = 0.0002), and the observed effect was higher in patients with MS than in healthy subjects. ALM‐exposed macrophages increased the proportion of T‐regulatory cells, without affecting the proportion of T‐effector cells. Neutralizing the CD23 + monocytes with antibodies reversed the effect specifically on the CD4 + CD39 + T‐regulatory cell subpopulation but not on the CD4 + CD25 hi CD127 lo FOXP3 + subpopulation. ALM induces the conversion of monocytes into anti‐inflammatory macrophages, which in turn promotes T‐regulatory cell enhancement, in a CD23‐dependent manner. These findings suggest that the mechanism of action of ALM is relevant to aspects of MS pathogenesis.