T cell vaccination therapy in an induced model of anti-RNP autoimmune glomerulonephritis.
To establish the relevance of targeting disease-associated T cells in anti-RNP-associated glomerulonephritis, mice developing nephritis following immunization with U1-70-kd small nuclear ribonucleoprotein (snRNP) were treated with a single dose of irradiated antigen-selected T cell vaccine. T cell receptor usage in nephritic kidneys revealed oligoclonal use of T Cell Receptor V Beta (TRBV) genes as previously found in spleens and lungs of immunized mice with pulmonary disease. The CDR3 regions from T cell isolates showed sequence homology to those in humans with anti-RNP autoimmunity. Following T cell vaccination, urinalysis returned to normal in 5/7 treated mice (71% response rate) whereas all mock-treated mice continued to have an active urinary sediment (Fisher's Exact p=0.02). An oligoclonal population of T cells homologous to those identified in humans with anti-RNP autoimmunity is implicated in disease pathogenesis, and T cell vaccination is associated with a high rate of clinical improvement in established nephritis.
Trivedi
Sapna
S
University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
Zang
YunJuan
Y
Culpepper
Schartess
S
Rosenbaum
Erica
E
Fernandez
Irina
I
Martinez
Laisel
L
Hoffman
Robert W
RW
Greidinger
Eric L
EL
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation; D022801:Complementarity Determining Regions / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D007678:Kidney Glomerulus / Q000473:pathology; D008181:Lupus Nephritis / Q000276:immunology / Q000473:pathology / Q000628:therapy* / Q000652:urine; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D016482:Urinalysis; D014611:Vaccination / Q000379:methods*
D001323:Autoantibodies; D022801:Complementarity Determining Regions; D006684:HLA-DR Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011993:Recombinant Fusion Proteins; D017412:Ribonucleoprotein, U1 Small Nuclear
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