Oligoclonally expanding gammadelta T lymphocytes induce IgA switching in IgA nephropathy.
The aetiology of IgA nephropathy (IgAN) is closely related with abnormality of mucosal immunity. We investigated the roles of gammadelta T cells in the regulation of IgA production by B cells in IgAN patients. The proportion of gammadelta T cells in peripheral blood mononuclear cells (PBMNC) was higher in IgAN patients than in the controls and was found to be correlated with the proportion of surface IgA-positive (sIgA+) B cells, which are precursors of IgA-secreting plasma cells. After in vitro PWM stimulation, sIgA expression on B cells and IgA production were significantly enhanced in PBMNC obtained from IgAN patients, whereas the enhancements were abolished by removal of gammadelta T cells from the PBMNC. Purified gammadelta T cells from IgAN patients induced surface IgA expression on naïve sIgD+ B cells more effectively than did alphabeta T cells. Moreover, stimulated gammadelta T cells from IgAN patients produced a larger amount of TGF-beta1, which is one of the main cytokines that induces IgA class switching on B cells, as compared with alphabeta T cells and control gammadelta T cells. The expanded gammadelta T cells from IgAN patients exclusively expressed Vgamma9, and the nucleotide sequences of junctional regions of Vgamma9 showed very limited TCR diversities. It was therefore concluded that gammadelta T cells, which are expanded in response to specific antigens, enhance IgA class switching on B cells in IgAN patients.
Toyabe
S
S
Department of Paediatrics, Niigata University School of Medicine, Niigata, Japan. toyabe@med.niigata-u.ac.jp
Harada
W
W
Uchiyama
M
M
D000293:Adolescent; D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology; D002648:Child; D002999:Clone Cells / Q000473:pathology; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D005922:Glomerulonephritis, IGA / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis*; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D008163:Luminescent Measurements; D008213:Lymphocyte Activation / Q000187:drug effects; D008211:Lymphocyte Cooperation; D008297:Male; D008969:Molecular Sequence Data; D011043:Pokeweed Mitogens / Q000494:pharmacology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology
D018076:DNA, Complementary; D007070:Immunoglobulin A; D011043:Pokeweed Mitogens; D016692:Receptors, Antigen, T-Cell, gamma-delta