INTRODUCTION: 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. METHODS: In-vitro functional assays were performed using leucocytes isolated from human peripheral blood. In-vivo studies were performed in C57BL6 mice. RESULT: 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. CONCLUSION: 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).
INTRODUCTION: 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. METHODS: In-vitro functional assays were performed using leucocytes isolated from human peripheral blood. In-vivo studies were performed in C57BL6 mice. RESULT: 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. CONCLUSION: 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).
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