Researchers designing antitumor treatments have long focused on eliciting tumor-specific CD8 cytotoxic T lymphocytes (CTL) because of their potent killing activity and their ability to reject transplanted organs. The resulting treatments, however, have generally been surprisingly poor at inducing complete tumor rejection, both in experimental models and in the clinic. Although a few scattered studies suggested that CD4 T "helper" cells might also serve as antitumor effectors, they have generally been studied mostly for their ability to enhance the activity of CTL. In this mouse study, we compared monoclonal populations of tumor-specific CD4 and CD8 T cells as effectors against several different tumors, and found that CD4 T cells eliminated tumors that were resistant to CD8-mediated rejection, even in cases where the tumors expressed major histocompatibility complex (MHC) class I molecules but not MHC class II. MHC class II expression on host tissues was critical, suggesting that the CD4 T cells act indirectly. Indeed, the CD4 T cells partnered with NK cells to obtain the maximal antitumor effect. These findings suggest that CD4 T cells can be powerful antitumor effector cells that can, in some cases, outperform CD8 T cells, which are the current "gold standard" effector cell IntroductionResearchers designing antitumor vaccines, or treatments involving transfers of activated antitumor cells, have long focused on methods to elicit tumor-specific CD8 CTLs, envisioning that their potent ability to kill tumor targets in vitro and to reject transplants in vivo would translate into equally potent antitumor activity in vivo. Although many of the resulting treatments have indeed been able to elicit CTLs that recognize tumor cells and/or tumor antigens in vitro, complete tumor regression has been achieved in only a minority of patients. [1][2][3][4][5] Animal models have generated similar results. In a few cases, the transfer of monoclonal T cell receptor transgenic (TCR Tg) CD8 T cells was able to clear small tumors, 6 but in most, the TCR Tg CD8 cells were ineffective without the addition of other aids. In short, though CD8 CTL can clear tumors, they most often do not, unless helped by additional treatments. [6][7][8][9][10][11][12] Over the last 25 years, a few studies have shown that CD4 T cells could also clear tumors completely independently of CD8s. [13][14][15][16][17] Nevertheless, CD4 T cells continue to be studied mainly for their role as helpers for CD8 CTL, 11,18,19 and it has even been suggested that tumor-specific CD4 T regulatory cells could act as suppressors of antitumor responses. 20 Thus, their potential as CD8-independent antitumor effectors has gained only a few proponents, [13][14][15][16][17][21][22][23][24] and only a few of the newly designed cancer vaccines incorporate antigens to stimulate CD4 cells, mostly to enhance their helper activity. 25,26 Most studies using adoptive transfer of tumor-specific T cells continue to focus entirely on CD8 cells. 2,3,[27][28][29][30] We decided to do a direc...

Transglutaminase (TGase) 2 is a ubiquitously expressed enzyme that modifies proteins by cross-linking or polyamination. An aberrant activity of TGase 2 has implicated its possible roles in a variety of diseases including age-related cataracts. However, the molecular mechanism by which TGase 2 is activated has not been elucidated. In this report, we showed that oxidative stress or UV irradiation elevates in situ TGase 2 activity. Neither the expression level nor the in vitro activity of TGase 2 appeared to correlate with the observed elevation of in situ TGase 2 activity. Screening a number of cell lines revealed that the level of TGase 2 activation depends on the cell type and also the environmental stress, suggesting that unrecognized cellular factor(s) may specifically regulate in situ TGase 2 activity. Concomitantly, we observed that human lens epithelial cells (HLE-B3) exhibited about 3-fold increase in in situ TGase 2 activity in response to the stresses. The activated TGase 2 catalyzed the formation of water-insoluble dimers or polymers of ␣B-crystallin, ␤B 2 -crystallin, and vimentin in HLE-B3 cells, providing evidence that TGase 2 may play a role in cataractogenesis. Thus, our findings indicate that in situ TGase 2 activity must be evaluated instead of in vitro activity to study the regulation mechanism and function of TGase 2 in biological and pathological processes.

We established an AQP4-Ab ELISA, which could be a potential monitoring tool of disease activity.

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