Natural human antibody and intravenous immunoglobulin regulation of T cell activation

D.A. Chow PhD, Y. Li MD, S Hebert, BSc

University of Manitoba, Winnipeg, Canada.

AIM. The homeostatic action of polyclonal natural antibody (NAb) is being investigated through the identification of their cell surface targets and mode of action in the regulation of T cells. METHODS. Previous evidence from murine models supported NAb surveillance of developing tumors, preneoplastic and PKC-activated cells. Now, human Jurkat T leukemia cells treated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) to generate variants were repeatedly selected in vitro for high binding of IgG plus IgM in pooled normal human serum or IgG in intravenous immunoglobulin (IVIg) to generate the J4.1 and JIg3.1 lines respectively, for comparison with parental cells. RESULTS. Both variants bound at least 45% more serum IgG plus IgM and IVIg than the parental line. Similar to the murine data, flow cytometry revealed higher variant binding of monoclonal antibodies against activation-associated molecules including CD25, and CD45RA that rises transiently about 1 day after T cell activation. Binding of anti-CD45RB and anti-pan CD45 were increased with anti-CD45RO binding unchanged or slightly decreased. Consistent with this, immunoblotting of whole cell lysates revealed more higher molecular weight isoforms of CD45. While expression of the early activation marker CD69 was decreased, CD134, an activation marker which appears about one day after activation, was increased. Binding was decreased for antibodies against CD122, CD3 and FAS. CONCLUSIONS. The data suggests that T cell markers that are increased about 1 day after activation are targets of normal human IgG and IgM. This argues that human IgG and IgM directly regulate T cells during an early, possibly transient stage of normal activation, which is important in inflammatory and autoimmune responses and for early neoplastic development.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Novel Therapies, Part 1.