Emergence of a type II collagen-specific helper T cell response.
Antigen-driven development of persistent self-reactive Th cells underlies the chronic, progressive nature of many autoimmune diseases. It is crucial to understand the behavior of these self-reactive Th cells; however, they have been notoriously difficult to isolate directly ex vivo. Collagen-induced arthritis (CIA) can be initiated in I-A(q)-expressing mice (DBA/1) using heterologous type II collagen (cII) immunization and is dependent on Th cells that are specific for a single immunodominant epitope. Here, we identify one compartment of cII-specific Th cell using TCR beta expression, cell surface phenotype, and direct single-cell repertoire analysis. A subpopulation of CD4(+)V beta 10(+) T cells up-regulates both CD44 and GL7 and expands significantly in response to initial priming in the majority of animals (D9: 70%). The cII-specific V beta 10(+) primary responders are further resolved through expression of a highly restricted junctional region, previously associated with autoimmune disease. This cII-specific clonotype rapidly re-expands upon antigen recall and can be isolated from the lymph nodes of arthritic animals. These single-cell analyses quantify the emergence, decline and rapid re-emergence of a self-reactive Th cell population in vivo and outline one strategy for isolating these cells directly ex vivo.
Pogue-Caley
R R
RR
Department of Immunology, Duke University Medical Center, Durham, NC 27704, USA.
McHeyzer-Williams
M G
MG
D000595:Amino Acid Sequence; D000818:Animals; D001168:Arthritis / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D001483:Base Sequence; D002999:Clone Cells / Q000276:immunology; D003094:Collagen / Q000276:immunology*; D022801:Complementarity Determining Regions / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D005434:Flow Cytometry; D007114:Immunization; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000276:immunology; D013379:Substrate Specificity; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*
D022801:Complementarity Determining Regions; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D003094:Collagen