Failure of Rearranged TCR Transgenes to Prevent Age-Associated Thymic Involution

Author:

Lacorazza H. Daniel1,Guevara Patiño Jose A.1,Weksler Marc E.23,Radu Dorel4,Nikolić-Z̆ugić Janko13

Affiliation:

1. *Laboratory of T Cell Development, Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021;

2. †Division of Geriatrics and Gerontology, Weill Medical College, and

3. ‡Weill Graduate School of Medical Sciences, Cornell University, New York, NY 10021; and

4. §Department of Microbiology, Mt. Sinai School of Medicine, New York, NY 10129

Abstract

AbstractAfter puberty, the thymus undergoes a dramatic loss in volume, in weight and in the number of thymocytes, a phenomenon termed age-associated thymic involution. Recently, it was reported that age-associated thymic involution did not occur in mice expressing a rearranged transgenic (Tg) TCRαβ receptor. This finding implied that an age-associated defect in TCR rearrangement was the major, if not the only, cause for thymic involution. Here, we examined thymic involution in three other widely used MHC class I-restricted TCRαβ Tg mouse strains and compared it with that in non-Tg mice. In all three TCRαβ Tg strains, as in control mice, thymocyte numbers were reduced by ∼90% between 2 and 24 mo of age. The presence or absence of the selecting MHC molecules did not alter this age-associated cell loss. Our results indicate that the expression of a rearranged TCR alone cannot, by itself, prevent thymic involution. Consequently, other presently unknown factors must also contribute to this phenomenon.

Publisher

The American Association of Immunologists

Subject

Immunology,Immunology and Allergy

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