Rescue of defective T cell development and function in Atm-/- mice by a functional TCRαβ transgene

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 TCR alpha beta transgene was introduced into these mutant mice. Analysis of the Atm(-/-)TCR alpha beta(+) mice indicated that the transgenic TCR alpha beta 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(-/-)TCR alpha beta(+) and control mice suggested that Atm is involved in the thymocyte expansion. Finally, evaluation of the T-dependent immune responses in Atm(-/-)TCR alpha beta(+) 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.