CD43 is a highly glycosylated transmembrane protein that regulates T cell activation. CD43-/- T cells are hyperproliferative and the cytoplasmic tail of CD43 has been found to be sufficient to reconstitute wild-type proliferation levels, suggesting an intracellular mechanism. In this study, we report that upon TCR ligation CD43-/- T cells demonstrated no increase in tyrosine phosphorylation but a decreased calcium flux. Interestingly, CD43-/- T cells preferentially differentiated into Th2 cells in vitro, and CD43-/- T cells show increased GATA-3 translocation into the nucleus. In vivo, CD43-/- mice exhibited increased inflammation in two separate models of Th2-mcdiated allergic airway disease. In contrast, in Th1-mediated diabetes, nono-bese diabetic CD43 -/- mice did not significantly differ from wild-type mice in disease onset or progression. Th1-induced experimental autoimmune encephalomyelitis to M0G35-55 was also normal in the CD43-/- mice. Nonetheless, the CD43-/-mice produced more IL-5 when restimulated with MOG 35-55 in vitro and demonstrated decreased delayed-type hypersensitivity responses. Together, these data demonstrate that although CD43-/- T cells preferentially differentiate into Th2 cells, this response is not sufficient to protect against Thl-mediated autoimmune responses.
ASJC Scopus subject areas
- Immunology and Allergy