Fig. 9. Steps where regulatory T-cell activity may shape arthritis development in TS1×HACII mice.

Step 1, Deletion/Treg cell formation among autoreactive 6.5+CD4+ thymocytes. Step 2, Lymphopenia-induced proliferation of 6.5+CD4+ T cells secondary to severe thymocyte deletion. Step 3, reciprocal activation of HA-specific CD4+ T cells by HA-expressing antigen presenting cells. Step 4, activation of B cells by HA-specific CD4+ T cells. Step 5, spontaneous differentiation and cytokine production by autoreactive HA-specific CD4+ T cells. Step 6, development of a regional immune response in the lymph nodes that drain the major joints.