Rescue of Defective T Cell Development and Function in Atm−/− Mice by a Functional TCRαβ Transgene

Abstract

The Atm−/− mice recapitulate most of the defects observed in ataxia-telangiectasia (A-T) patients, including a high incidence of lymphoid tumors and immune defects characterized by defective T cell differentiation, thymus hypoplasia, and defective T-dependent immune responses. To understand the basis of the T cell developmental defects in Atm−/− mice, a functional TCRαβ transgene was introduced into these mutant mice. Analysis of the Atm−/−TCRαβ+ mice indicated that the transgenic TCRαβ can rescue the defective T cell differentiation and partially rescue the thymus hypoplasia in Atm−/− mice, indicating that thymocyte positive selection is normal in the Atm−/− mice. In addition, cell cycle analysis of the thymocytes derived from Atm−/−TCRαβ+ and control mice suggested that Atm is involved in the thymocyte expansion. Finally, evaluation of the T-dependent immune responses in Atm−/−TCRαβ+ mice indicated that Atm is dispensable for normal T cell function. Therefore, the defective T-dependent immune responses in Atm−/− mice must be secondary to greatly reduced T cell numbers in these mutant mice.