Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease

• DOI: 10.1073/pnas.0403342101
• Publication Date: 2004-07-03T00:42:22Z
• Authors: Silke Paust; Linrong Lu; Nami McCarty; Harvey Cantor
• Keywords: CD4-Positive T-Lymphocytes; 0301 basic medicine; Mice, Inbred BALB C; Wasting Syndrome; Gene Expression; In Vitro Techniques; Mice, Mutant Strains; Autoimmune Diseases; 3. Good health; DNA-Binding Proteins; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Retroviridae; 0302 clinical medicine; Lymphopenia; B7-1 Antigen; Animals; Signal Transduction

Although there is considerable evidence that a subpopulation of regulatory CD4 + CD25 T cells can suppress the response autoreactive cells, underlying molecular mechanism not understood. We find transmission suppressive signal by CD4CD25 requires engagement B7 molecule expressed on target cells. The from B7-deficient mice resistant to suppression in vitro , and these provoke lethal wasting disease lymphopenic despite presence Susceptibility restored lentiviral-based expression full-length, but truncated, lacking transmembrane/cytoplasmic domain. Because truncation mutants restores CD28-dependent costimulatory activity, findings indicate B7-based activity suggest new approaches modifying autoimmune responses.