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Rescue of Defective T Cell Development and Function in Atm^-/- Mice by a Functional TCRß Transgene¹

Department of Biology, University of California, San Diego, La Jolla, CA 92093

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

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