Abstract: Compounds, compositions, and methods for generating T cells with altered phenotype are disclosed. The phenotype-altered T cells have increased persistence, prolonged survival, and increased antitumor activity and are useful for treatment of cancers.

Abstract: The embodiments provide for the modulation of both the differentiation and activity of human TH17 cells. More specifically, human TH17 cell differentiation can modulated by TGF-? and IL-21, and their agonists and antagonists. Function of TH17 cells can be modulated by, for example, BLT1 or podoplanin, and their agonists and antagonists. Additionally, the embodiments provide for the identification of TH17 cells. More specifically, human TH17 cells specifically upregulate BLT1 and podoplanin.

Abstract: The embodiments provide for the modulation of both the differentiation and activity of human Th17 cells. More specifically, human Th17 cell differentiation can modulated by TGF-? and IL-21, and their agonists and antagonists. Function of Th17 cells can be modulated by, for example, BLT1 or podoplanin, and their agonists and antagonists. Additionally, the embodiments provide for the identification of Th17 cells. More specifically, human Th17 cells specifically upregulate BLT1 and podoplanin.

Abstract: The embodiments provide for the modulation of both the differentiation and activity of human Th17 cells. More specifically, human Th17 cell differentiation can modulated by TGF-? and IL-21, and their agonists and antagonists. Function of Th17 cells can be modulated by, for example, BLT1 or podoplanin, and their agonists and antagonists. Additionally, the embodiments provide for the identification of Th17 cells. More specifically, human Th17 cells specifically upregulate BLT1 and podoplanin.

Abstract: The embodiments provide for the modulation of both the differentiation and activity of human TH17 cells. More specifically, human TH17 cell differentiation can modulated by TGF-? and IL-21, and their agonists and antagonists. Function of TH17 cells can be modulated by, for example, BLT1 or podoplanin, and their agonists and antagonists. Additionally, the embodiments provide for the identification of TH17 cells. More specifically, human TH17 cells specifically upregulate BLT1 and podoplanin.

Abstract: This invention demonstrates that KRC molecules have multiple important functions as modulating agents in regulating a wide variety of cellular processes including: inhibiting NFkB transactivation, increasing TNF-alpha induced apoptosis, inhibiting JNK activation, inhibiting endogenous TNF-alpha expression, promoting immune cell proliferation and immune cell activation (e.g., in Th1 cells), activating IL-2 expression e.g., by activating the AP-1 transcription factor, and increasing actin polymerization. The present invention also demonstrates that KRC interacts with TRAF. Furthermore, the present invention demonstrates that KRC physically interacts with the c-Jun component of AP-1 to control its degradation Methods for identifying modulators of KRC activity are provided. Methods for modulating an immune response using agents that modulate KRC activity are also provided.

Abstract: This invention demonstrates that KRC molecules have multiple important functions as modulating agents in regulating a wide variety of cellular processes including: inhibiting NFkB transactivation, increasing TNF-alpha induced apoptosis, inhibiting JNK activation, inhibiting endogenous TNF-alpha expression, promoting immune cell proliferation and immune cell activation (e.g., in Th1 cells and/or Th2), activating IL-2 expression e.g., by activating the AP-1 transcription factor, and increasing actin polymerization. The present invention also demonstrates that KRC interacts with TRAF. Furthermore, the present invention demonstrates that KRC physically interacts with the c-Jun component of AP-1 to control its degradation. The present invention also demonstrates that KRC is downstream of several lymphocyte membrane receptors, including TNFR, TCR and TGF?R. Upon TNFR signaling, KRC associates with the adaptor protein TRAF2 to inhibit NFKB and JNK-dependent gene expression.

Abstract: The invention demonstrates that NFATp and NFAT4 are required for the control of lymphocyte homeostasis and act as selective repressors of Th2 cells. The invention provides mice deficient in both NFATp and NFAT4 that exhibit a phenotype characteristic of increased Th2 cell activity. Methods for identifying modulators of Th2 cell activity, using either cells deficient in both NFATp and NFAT4, mice deficient in both NFATp and NFAT4, or indicator compositions containing both NFATp and NFAT4, are provided. Methods of regulating Th2 cell activity using agents that modulate the activity of NFATp and NFAT4 are also provided. Methods for diagnosing disorders associated with aberrant Th2 cell activity, by assessing changes in NFATp and/or NFAT4 expression, are also provided.

Abstract: This invention demonstrates that KRC molecules have multiple important functions as modulating agents in regulating a wide variety of cellular processes including: inhibiting NFkB transactivation, increasing TNF-alpha induced apoptosis, inhibiting JNK activation, inhibiting endogenous TNF-alpha expression, promoting immune cell proliferation and immune cell activation (e.g., in Th1 cells), activating IL-2 expression e.g., by activating the AP-1 transcription factor, and increasing actin polymerization. The present invention also demonstrates that KRC interacts with TRAF. Furthermore, the present invention demonstrates that KRC physically interacts with the c-Jun component of AP-1 to control its degradation Methods for identifying modulators of KRC activity are provided. Methods for modulating an immune response using agents that modulate KRC activity are also provided.

Abstract: The invention demonstrates that NFATp and NFAT4 are required for the control of lymphocyte homeostasis and act as selective repressors of Th2 cells. The invention provides mice deficient in both NFATp and NFAT4 that exhibit a phenotype characteristic of increased Th2 cell activity. Methods for identifying modulators of Th2 cell activity, using either cells deficient in both NFATp and NFAT4, mice deficient in both NFATp and NFAT4, or indicator compositions containing both NFATp and NFAT4, are provided. Methods of regulating Th2 cell activity using agents that modulate the activity of NFATp and NFAT4 are also provided. Methods for diagnosing disorders associated with aberrant Th2 cell activity by assessing changes in NFATp and/or NFAT4 expression, are also provided.