title: γδ T cells affect IL-4 production and B-cell tolerance.
abstract: γδ T cells can influence specific antibody responses. Here, we report that mice deficient in individual γδ T-cell subsets have altered levels of serum antibodies, including all major subclasses, sometimes regardless of the presence of αβ T cells. One strain with a partial γδ deficiency that increases IgE antibodies also displayed increases in IL-4-producing T cells (both residual γδ T cells and αβ T cells) and in systemic IL-4 levels. Its B cells expressed IL-4-regulated inhibitory receptors (CD5, CD22, and CD32) at diminished levels, whereas IL-4-inducible IL-4 receptor α and MHCII were increased. They also showed signs of activation and spontaneously formed germinal centers. These mice displayed IgE-dependent features found in hyper-IgE syndrome and developed antichromatin, antinuclear, and anticytoplasmic autoantibodies. In contrast, mice deficient in all γδ T cells had nearly unchanged Ig levels and did not develop autoantibodies. Removing IL-4 abrogated the increases in IgE, antichromatin antibodies, and autoantibodies in the partially γδ-deficient mice. Our data suggest that γδ T cells, controlled by their own cross-talk, affect IL-4 production, B-cell activation, and B-cell tolerance.
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206;
authors.forename: Yafei
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Immunology & Microbiology, University of Colorado Health Sciences Center, Aurora, CO 80045;
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Heiser
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206;
authors.forename: Thiago O
authors.initials: TO
authors.lastname: Detanico
authors.affiliation: Department of Immunology & Microbiology, University of Colorado Health Sciences Center, Aurora, CO 80045;
authors.forename: Andrew
authors.initials: A
authors.lastname: Getahun
authors.affiliation: Department of Immunology & Microbiology, University of Colorado Health Sciences Center, Aurora, CO 80045;
authors.forename: Greg A
authors.initials: GA
authors.lastname: Kirchenbaum
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206;
authors.forename: Tamara L
authors.initials: TL
authors.lastname: Casper
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206;
authors.forename: M Kemal
authors.initials: MK
authors.lastname: Aydintug
authors.affiliation: The Institute of Food Research and Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7JT, United Kingdom; and.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Carding
authors.affiliation: Laboratory of Biological Protection, Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Ikuta
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206;
authors.forename: Hua
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Immunology & Microbiology, University of Colorado Health Sciences Center, Aurora, CO 80045; Department of Biomedical Research, National Jewish Health, Denver, CO 80206;
authors.forename: John C
authors.initials: JC
authors.lastname: Cambier
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206; Department of Immunology & Microbiology, University of Colorado Health Sciences Center, Aurora, CO 80045;
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Wysocki
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206; Department of Immunology & Microbiology, University of Colorado Health Sciences Center, Aurora, CO 80045;
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: O'Brien
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206; Department of Immunology & Microbiology, University of Colorado Health Sciences Center, Aurora, CO 80045; bornw@njhealth.org.
authors.forename: Willi K
authors.initials: WK
authors.lastname: Born
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000906:Antibodies / Q000097:blood; D001323:Autoantibodies / Q000097:blood; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D005260:Female; D018858:Germinal Center / Q000378:metabolism; D007108:Immune Tolerance; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood; D015847:Interleukin-4 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000276:immunology; D008810:Mice, Inbred C57BL; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013154:Spleen / Q000166:cytology
chemical_list: D000906:Antibodies; D001323:Autoantibodies; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015847:Interleukin-4; D007073:Immunoglobulin E
keywords: autoimmunity; gammadelta T cell; immunoglobulin; interleukin-4; tolerance