Failure of rearranged TCR transgenes to prevent age-associated thymic involution

After puberty, the thymus undergoes a dramatic loss in volume, in weight an d in the number of thymocytes, a phenomenon termed age-associated thymic in volution, Recently, it was reported that age-associated thymic involution d id not occur in mice expressing a rearranged transgenic (Tg) TCR alpha beta receptor. This finding implied that an age-associated defect in TCR rearra ngement was the major, if not the only, cause for thymic involution. Here, we examined thymic involution in three other widely used MHC class I-restri cted TCR alpha beta Tg mouse strains and compared it with that in non-Tg mi ce. In all three TCR alpha beta Tg strains, as in control mice, thymocyte n umbers were reduced by similar to 90% between 2 and 24 mo of age. The prese nce or absence of the selecting MHC molecules did not alter this age-associ ated cell loss, Our results indicate that the expression of a rearranged TC R alone cannot, by itself prevent thymic involution, Consequently, other pr esently unknown factors must also contribute to this phenomenon.