EVIDENCE FOR DOWN-REGULATION OF HIGHLY EXPRESSED TCR BY CD4 AND CD45 ON NONSELECTED CD4(+)CD8(+) THYMOCYTES

Immature CD4(+)CD8(+) double-positive (DP) thymocytes are positively s elected for further development if they express TCR reacting with thym ic ligands of low affinity, However, the majority of DP thymocytes exp ress low TCR levels. This low level of TCR may be insufficient to reco gnize thymic ligands. To understand the basis for the low expression o f TCR on DP thymocytes, we determined the density of TCR expression at various stages of their development using TCR transgenic (TCR-Tg) mic e, We found that TCR expression was high in the thymocytes that had re cently transited into the DP stage but then gradually decreased on DP cells if they were not selected by TCR interaction with MHC molecules, However, such TCR suppression was not observed in positively selected DP cells and in the non-selected DP cells obtained from CD45 deficien t mice or from mice receiving anti-CD4 mAb, These findings suggest tha t the once highly expressed TCR at the DP stage is suppressed by CD45 and/or CD4 on non-selected thymocytes, Furthermore, TCR suppression is prevented by TCR-mediated signals, The maintenance of high TCR levels on positively selected DP thymocytes may facilitate their selection.