IL-4 and T cells are required for the generation of IgG1 isotype antibodies against cardiolipin.
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 alphabeta TCR(+), gammadelta 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.
Fischer
Karsten
K
Department of Immunology, Max-Planck-Institute for Infection Biology, Berlin, Germany.
Collins
Helen
H
Taniguchi
Masaru
M
Kaufmann
Stefan H E
SH
Schaible
Ulrich E
UE
D000818:Animals; D017153:Antibodies, Anticardiolipin / Q000096:biosynthesis* / Q000097:blood; D000936:Antigen-Antibody Complex / Q000008:administration & dosage / Q000276:immunology; D002308:Cardiolipins / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D007106:Immune Sera / Q000378:metabolism; D007115:Immunization Schedule; D017578:Immunoglobulin Class Switching / Q000235:genetics; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007279:Injections, Subcutaneous; D015847:Interleukin-4 / Q000502:physiology*; D050356:Lipid Metabolism; D008055:Lipids / Q000276:immunology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D009169:Mycobacterium tuberculosis / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000473:pathology / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology; D014376:Tuberculosis / Q000276:immunology
D017153:Antibodies, Anticardiolipin; D000936:Antigen-Antibody Complex; D002308:Cardiolipins; D007106:Immune Sera; D007074:Immunoglobulin G; D008055:Lipids; D015847:Interleukin-4