Immunochimie et immunopathologie

Role of the CD62L Expression Pathway in the IVIg Inhibition of Cytotoxic T Cell Responses

Abstract

Dominique Chabot, Patrick Trépanier, Cassandra Ringuette-Goulet, Lionel Loubaki and Renée Bazin

Intravenous immunoglobulin (IVIg) is successfully used in the treatment of a number of immune-mediated disorders, including diseases in which self-reactive cytotoxic CD8+ T lymphocytes (CTLs) play an important pathological role. However, the exact molecular and cellular mechanisms underlying its effects on the cytotoxic response remain undefined. Using a mouse model of ovalbumin (OVA) immunization, we recently showed that IVIg treatment decreases the in vivo generation of OVA-specific CD8+ T cells, as well as the proportion of CTLs expressing the extracellular cytotoxic marker CD107a. In the present work, we demonstrate that during the course of an active immune response in mice, IVIg treatment is associated with the presence of splenic CD8+ T cells expressing high levels of CD62L and by an increased plasma concentration of soluble CD62L. Because cell surface expression of CD62L negatively correlates with the cytotoxic activity of CD8+ T cells and that soluble CD62L exhibits anti-inflammatory effects, we herein propose that the CD62L expression pathway plays a key role in the therapeutic effects of IVIg in CD8-mediated autoimmune and inflammatory disorders.