Positive selection of thymocytes: the long and winding road

Transgenic Expression of RasGRP1 Induces the Maturation of Double-Negative Thymocytes and Enhances the Production of CD8 Single-Positive Thymocytes

“…6). The CD69 Ϫ CD62L ϩ phenotype of the majority of transgenic CD8 SP cells further indicates that they are relatively mature (44,45). In contrast to CD8 SP cells, the CD4 SP thymocytes of RasGRP1 transgenic mice were equivalent to those of normal mice in terms of CD3, HSA, CD69, and CD62L expression (Figs.…”

Expression of 4-1BB and 4-1BBL in thymocytes during thymus regeneration

“…TCR complexes are not only vital for the functioning of mature T lymphocytes, but are also (Lucas and Germain, 1996;Anderson et al, 1999). 4-1BB and 4-1BBL expression on developing T cells during thymus regeneration agreed with these sequences, suggesting that 4-1BB and 4-1BBL may be involved in the differentiation of the thymocytes.…”

“…Positive selection is a key step in T cell development because it leads to the survival of CD4 + CD8 + DP thymocytes already pre-programmed to undergo differentiation, and also provides essential differentiation-inducing signals (Anderson et al, 1997(Anderson et al, , 1999. It is well documented that TCRmediated signals induce many phenotypic changes during the positive selection, including up-regulation of TCR expression on DP thymocytes, termination of the activities of the recombinationactivating genes (RAG-1 and RAG-2), expression of CD69, and down-regulation of either CD4 or CD8 (Turka et al, 1991;Borgulya et al, 1992;Brändle et al, 1992Brändle et al, , 1994Bendelac et al, 1992;Swat et al, 1993;Yamashita et al, 1993;Anderson et al, 1997Anderson et al, , 1999Correia-Neves et al, 2001).…”

“…It is well documented that TCRmediated signals induce many phenotypic changes during the positive selection, including up-regulation of TCR expression on DP thymocytes, termination of the activities of the recombinationactivating genes (RAG-1 and RAG-2), expression of CD69, and down-regulation of either CD4 or CD8 (Turka et al, 1991;Borgulya et al, 1992;Brändle et al, 1992Brändle et al, , 1994Bendelac et al, 1992;Swat et al, 1993;Yamashita et al, 1993;Anderson et al, 1997Anderson et al, , 1999Correia-Neves et al, 2001). In agreement with the two-signal hypothesis for T cell activation it has been shown that interactions between the TCR and MHC-peptide complexes are not enough to induce complete maturation of CD4 + CD8 + DP thymocytes, suggesting that additional accessory signals are required (Groves et al, 1997;Anderson et al, 1999). In particular, the costimulatory molecules that participate in the initial phases of positive selection have not yet been identified, although some molecules expressed by CD4 + CD8 + DP thymocytes, such as CD2, CD5, CD24, CD28, CD49d, CD81 and thymic shared antigen 1 (TSA-1), have been shown to possess costimulatory activity in vitro in the absence of thymic epithelium, suggesting that these accessory molecules are involved in positive selection (Cibotti et al, 1997;Anderson et al, 1999).…”

Deregulated expression of RasGRP1 initiates thymic lymphomagenesis independently of T-cell receptors

“…However, another marker of T-cell activation, loss of CD62L expression (Dailey, 1998), did not accompany thymocyte transformation in RasGRP1 transgenic thymocytes ( Figure 2d). Activation of DP thymocytes via positively selecting TCR triggers increased expression of CD69 and CD5 (Azzam et al, 1998;Anderson et al, 1999), but both of these markers were low in transformed DP thymocytes ( Figure 2d). Therefore, while the transformed DP thymocytes are activated in terms of being proliferative and enlarged, they do not express a full set of markers associated with TCR-dependent activation.…”