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IL-4 and T Cells Are Required for the Generation of IgG1 Isotype Antibodies Against Cardiolipin¹

Karsten Fischer^*,, Helen Collins^*, Masaru Taniguchi, Stefan H. E. Kaufmann^* and Ulrich E. Schaible^2,*

^* Department of Immunology, Max-Planck-Institute for Infection Biology, Berlin, Germany; Department of Biology, Chemistry, Pharmacy, Free University Berlin, Berlin, Germany; and Division of Molecular Immunology, Center for Biomedical Science, School of Medicine, Chiba University, Chiba, Japan

Infection with Mycobacterium tuberculosis induces Abs against a vast array of mycobacterial lipids and glycolipids. One of the most prominent lipid Ags recognized is cardiolipin (CL). The kinetics of the generation of anti-CL Abs during infection reveals that IgM titers to CL increase over time. Interestingly, at day 30 postinfection CL-specific IgG1 appears, an isotype usually dependent on T cell help. Using an immunization schedule with CL/anti-CL Ab complexes, which induces antiphospholipid syndrome in mice, we show that the generation of IgG1 to CL requires IL-4 and that optimal production is T cell dependent. IgG1 production to CL was impaired in nude (nu/nu) mice devoid in conventional T cells, but was not affected in mice deficient for either TCR⁺, TCR⁺, CD4⁺, CD8⁺, or NK1.1⁺ T cells. We conclude that IgG1 production to CL depends on T cell help and IL-4, which can be provided by different T cell populations. This is the first report that IL-4 is indispensable for the induction of IgG1 Abs to lipid Ags.

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				K. Fischer, E. Scotet, M. Niemeyer, H. Koebernick, J. Zerrahn, S. Maillet, R. Hurwitz, M. Kursar, M. Bonneville, S. H. E. Kaufmann, et al. Mycobacterial phosphatidylinositol mannoside is a natural antigen for CD1d-restricted T cells PNAS, July 20, 2004; 101(29): 10685 - 10690. [Abstract] [Full Text] [PDF]