Age-associated changes in CD90 expression on thymocytes and in TCR-dependent stages of thymocyte maturation in male rats
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To elucidate the effects of ageing on T-cell-maturation, in 3- and 18-month-old rats, we analysed the expression of: (i) CD4/CD8/TCR alpha beta and (ii) Thy-1, which is supposed to be a regulator of TCR alpha beta signalling, and thereby the thymocyte selection thresholds. Since an essential role for TCR alpha beta signalling in the development of CD4+25+T-reg-cells was suggested, the frequency of these cells was also quantified. We demonstrated that, as for mice, early thymocyte differentiational steps within the CD4-8- double negative (DN) developmental stage are age-sensitive. Furthermore, we revealed that TCRao-dependent stages of T-cell development are affected by ageing, most likely due to an impaired expression of Thy-1 on TCR alpha beta(low) thymocytes entering selection processes. The diminished frequency of the post-selection CD4+8+ double positive (DP) cells in aged rats, together with an overrepresentation of mature single positive (SP) cells, most probably suggests more ef...ficient differentiational transition from the DP TCR alpha beta(high) to the SP TCR alpha beta(high) developmental stage, which is followed by an increase in pre-migration proliferation of the mature SP cells. Moreover, the study indicated impaired intrathymic generation of CD4+25+T-reg-cells in aged rats, thus providing a possible explanation for the increased frequency of autoimmune diseases in ageing.
Keywords:ageing / T-cell differentiation / CD90 expression / thymocyte apoptosis / ConA / CD4+25+thymocytes
Source:Experimental Gerontology, 2006, 41, 6, 574-589
- Pergamon-Elsevier Science Ltd, Oxford