[12] However, immunoscope analysis showed a similar pattern betwe

[12] However, immunoscope analysis showed a similar pattern between CD8+ CD122+ CD49dhigh cells obtained from MLNs (Fig. 3a) and spleens (Fig. 3b), which suggests that the results from flow cytometric analysis were the result of the lower sensitivity of this technique compared

with immunoscope analysis. CD8+ CD122+ CD49dhigh cells display a different use of their TCR from other CD8+ T-cell populations. Such limited diversity is probably generated by clonal expansion buy RG7204 of mature CD8+ CD122+ CD49dhigh cells in the periphery rather than by preferential formation of TCR diversity in the thymus because such skewing of TCR diversity is not observed in the same CD8+ CD122+CD49dhigh cell population obtained from neonatal (4-day-old) mice. We investigated whether CD8+ CD122+CD49dhigh cells carrying the characteristic

TCR are preferentially selected in the thymus or expanded in the periphery. The data obtained from analysing neonate spleen T cells suggest that they expanded in the periphery during the course MG132 of immune constitution (Fig. 5). In neonates, lymphopenia-induced homeostatic proliferation occurs, which leads to generation of T cells with an activated phenotype,[29] CD8+ CD122+ Treg cells may recognize these activated T cells and expand during this period. Understanding TCR diversity is of considerable importance. Several studies have examined TCR diversity of CD4+ CD25+ Foxp3+ Treg cells.[30, 31] In neutral conditions, the TCR of CD4+ CD25+ Foxp3+ Treg cells is diverse.[32, 33] We found characteristically skewed TCR use in CD8+ CD122+ CD49dhigh cells, which is different from that in CD4+ CD25+ Foxp3+ Treg cells. Sulfite dehydrogenase Although we have not identified the mechanism underlying such skewed TCR use in CD8+ CD122+ CD49dhigh cells, and possibly in CD8+ CD122+ CD49dlow cells as well, one possibility is that CD8+ CD122+ CD49dhigh cells and/or CD8+ CD122+ CD49dlow cells may be constantly making contact with activated T cells that are also constantly generated because of exposure to exogenous antigens. In a previous study,

we proposed that CD8+ CD122+ Treg cells recognize antigens selectively expressed in activated T cells to exceed regulatory activity.[34] On the basis of this hypothesis, we may be able to identify the target antigen recognized by CD8+ CD122+ Treg cells with the traditional method used for cytotoxic T lymphocytes, i.e. expression cloning from a cDNA library prepared from target cells. To study the characteristic TCR of CD8+ CD122+ Treg cells, namely that of Vβ13+ cells, will lead to the identification of their target antigen, which may provide insight into understanding their function. By comparing the immunoscopic profile between CD8+ CD122+ CD49d+ cells and CD8+ CD122− cells using Vβ13 and Jβ primers, there are some skewing peaks in CD8+ CD122+ CD49d+ cells but they do not appear to be clonal or oligoclonal.

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