Naturally occurring IgM anti-leukocyte autoantibodies inhibit T-cell activation and chemotaxis

Naturally occurring IgM antileukocyte autoantibodies (IgM-ALA) are present from birth and increase during inflammatory processes of diverse etiologies. The clinical observation demonstrating a significant correlation (P < 01) between lack of acute rejections and presence of high levels of IgM-ALA in recipients of kidney allografts prompted us to study if IgM-ALA alters T-cell function and leukocyte chemotaxis.

In-vitro functional assays were performed using leucocytes isolated from human peripheral blood. In-vivo studies were performed in C57BL6 mice.

Human studies revealed that IgM-ALA consist of several different IgM, each with specificities for a different leukocyte receptor, e.g., CD3, CD4, CCR5, and CXCR4. We show that IgM inhibits T-cell activation, proliferation, and chemotaxis. Data on in vivo murine models of ischemia-reperfusion injury and cardiac transplantation support our hypothesis.

The innate anti-inflammatory mechanism of IgM-ALA can be exploited by using purified normal IgM to inhibit inflammatory states or by a vaccine approach to increase in vivo production of IgM-ALA (e.g., prior to a transplant).