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LETTERS TO THE EDITOR |
Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115
We recently described that CD226 is specifically expressed on differentiated Th1 T cells (1). Using a novel rat 10E5 mAb, we find that 
40% of CD4+T cells purified from the spleen of C57BL/6 express CD226. Upon activation, CD226 is up-regulated on all CD4+ T cells, independent of their Th phenotype, which is consistent with the results reported by Shibuya et al. (2). Interestingly, CD226 is also highly expressed on CD4+ T cells in the absence of any polarization after early rounds of in vitro stimulation (see Fig. 4 in Ref.1).
Although CD226 is expressed on the majority of activated T cells, our data demonstrates that after multiple rounds of polarization in vitro, CD226 expression is down-regulated on Th2 and Th0 cells and up-regulated on Th1 T cells. Consistent with this observation, long-term Th1 T cell clones such as AE7, 7A5, or 2D2 express CD226, whereas CD226 is undetectable on Th0 or Th2 clones (see Fig. 4 in Ref.1).
Shibuya et al. have generated a series of rat mAbs against CD226, TX-42, TX-43, and TX-44. Using the TX-42 mAb, they observe that CD226 is expressed on both IFN-
and IL-4-secreting T cells activated for 4 h with PMA/ionomycin isolated from either BALB/c or C57BL/6 mice (see Fig. 1B in Ref.2). This finding is not in conflict with our results since we also show an up-regulation of CD226 upon T cell activation, as well as strong expression of CD226 on T cells secreting either IL-4 and IFN- or both (Th0 condition) during early rounds of in vitro activation and polarization (see Figs. 3 and 4 in Ref.1).
Furthermore, the discrepancy in the expression of CD226 on Th1 and Th2 lines, as observed by Shibuya et al., and data we presented in our article could be due to the specificity of Abs used in the two studies. Three alternative splice forms have been identified for murine CD226 on the mRNA level, and it is possible that the 10E5 mAb and those generated by Shibuya et al. are specific for different isoforms. It remains to be seen whether the isoforms are differentially expressed in terminally differentiated Th1 and Th2 cells.
Finally, Shibuya et al. also describe that using either of their mAbs they are able to stain at least 80% of the naive CD4+ T cells. In our hands, only 40% of the naive CD4+ T cells were stained with 10E5 mAb, and this difference could be due to the affinity of the Abs or due to specificity for different isoforms of CD226 recognized by the two Abs.
In summary, we do not see a conflict in the data reported by us and those presented by Shibuya et al. Like Shibuya et al., we show that both IFN--producing Th1 cells and IL-4-producing Th2 cells express CD226 on their cell surface early during T cell differentiation. However, after multiple rounds of polarization, Th2 and Th0 cells show a dramatic drop in the cell surface expression of CD226. In contrast Th1 cells retain or up-regulate the expression of CD226.
References
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