Limited T-cell receptor diversity predisposes to Th2 immunopathology: involvement of Tregs and conventional CD4 T cells.

INTRODUCTION: A variety of immunodeficiencies characterized by limitations in the T-cell repertoire are also associated with Th2-like immunopathology. METHODS: We established a model of this phenomenon by transferring limited numbers of mature CD4+ T-cells into lymphopenic mice. RESULT: This transfer resulted in eosinophilic pneumonia with alternatively activated macrophages, eosinophilic gastritis, and other organ infiltration, associated with elevated IgE levels and Th2 cytokine production by the transferred cells. Transfer of large numbers of T-cells did not result in any pathology. The disease could be suppressed by CD25+ Foxp3+ regulatory T cells, but only when the T-cell receptor repertoire of the Tregs was diverse. CONCLUSION: Collectively, the data suggest that limited T-cell receptor repertoires derived from normal CD4+ T cells can cause severe Th2 immunopathology, and that failure of control by Tregs due to limitation of their repertoire is partially responsible for this phenotype.