Elevated direct and IgM enhanced ADCC activity in multiple sclerosis patients
Merrill, J.E.; Wåhlin, B.; Sidén, A.; Perlmann, P.
Journal of Immunology 128(4): 1728-1735
1982
ISSN/ISBN: 0022-1767 PMID: 7037955 Document Number: 195952
Cells from peripheral blood lymphocytes (PBL) of multiple sclerosis (MS) patients were compared to PBL from age- and sex-matched controls for their ability to mediate antibody-dependent cellular cytotoxicity (ADCC) against ox erythrocytes (ORBC). Cytotoxicity was assayed by 51Cr release and, at the cellular level, by an ADCC-plaque assay. On the average, PBL of MS patients (especially those in acute and chronic stage of disease) had higher ADCC activity than control PBL. The surface marker profile of the peripheral blood killer (K) cells mediating IgG-dependent ADCC in MS patients indicated that MS patients in comparison with controls had a higher proportion of T cell-like K cells bearing Helix pomatia receptors, Fc receptors for IgM, i.e., TGM [T cell with Fc receptors for both IgG and IgM] and T cell-specific antigens as defined by the monoclonal antibodies OKT4, OKT3 and Leu 1. The number of K cells reacting with the monocyte/null cell-specific antibody OKM1 and with the T suppressor/CTL-specific antibody Leu 2a was the same in MS and controls. In accord with the finding of significantly higher proportions of K cells in the patients' PBL than in the controls, patients' K cells could also mediate optimal ADCC at a 10-fold lower concentration of IgG. K cells of MS PBL could mediate IgM-enhanced, IgG-dependent ADCC to a greater extent than control PBL. The index of enhancement by nonlytic concentrations of IgM was higher and the IgM enhanced killing could be titrated to lower concentrations of both IgM and IgG in MS PBL, reflecting the occurrence of significantly increased proportions of FcGMR[Fc receptors for both IgG and IgM]positive T effector cells in these patients. The possibility of in vivo activation of FcR-positive cytotoxic cells in MS patients and the biologic implications of an immunoregulatory role of ADCC mediated at suboptimal concentrations of IgG are discussed.