Antigen-driven development of persistent self-reactive Th cells underlies t
he chronic, progressive nature of many autoimmune diseases. It is crucial t
o understand the behavior of these self-reactive Th cells; however, they ha
ve been notoriously difficult to isolate directly ex vivo. Collagen-induced
arthritis (CIA) can be initiated in I-A(q)-expressing mice (DBA/1) using h
eterologous type II collagen (cII) immunization and is dependent on Th cell
s that are specific for a single immunodominant epitope. Here, we identify
one compartment of cll-specific Th cell using TCR beta expression, cell sur
face phenotype, and direct single-cell repertoire analysis. A subpopulation
of CD4(+)V beta 10(+) T cells up-regulates both CD44 and GL7 and expands s
ignificantly in response to initial priming in the majority of animals (D9:
70%). The cll-specific V beta 10(+) primary responders are further resolve
d through expression of a highly restricted junctional region, previously a
ssociated with autoimmune disease. This cII-specific clonotype rapidly re-e
xpands upon antigen recall and can be isolated from the lymph nodes of arth
ritic animals. These single-cell analyses quantify the emergence, decline a
nd rapid re-emergence of a self-reactive Th cell population in vivo and out
line one strategy for isolating these cells directly ex vivo.