Cannabinol Enhancement of Interleukin-2 (IL-2) Expression by T Cells Is Associated with an Increase in IL-2 Distal Nuclear Factor of Activated T Cell Activity

ABSTRACT Mice immunized with two different cryptococcal antigen preparations, one a soluble culture filtrate antigen (CneF) in complete Freund’s adjuvant (CFA) and the other heat-killed Cryptococcus neoformans cells (HKC), develop two different profiles of activated T cells. CneF-CFA induces CD4+ T cells responsible for delayed-type hypersensitivity (DTH) reactivity and for amplification of the anticryptococcal DTH response, whereas HKC induce CD4+ and CD8+ T cells involved in anticryptococcal DTH reactivity and activated T cells which directly kill C. neoformans cells. The main purpose of this study was to assess the level of protection afforded by each of the two different T-cell profiles against challenge with viable C. neoformans cells, thereby identifying which activated T-cell profile provides better protection. CBA/J mice immunized with CneF-CFA had significantly better protective responses, based on better clearance of C. neoformans from tissues, on longer survival times, and on fewer and smaller lesions in the brain, than HKC-immunized mice or control mice similarly infected with C. neoformans. Both immunization protocols induced an anticryptococcal DTH response, but neither induced serum antibodies to glucuronoxylmannan, so the protection observed in the CneF-CFA immunized mice was due to the activated T-cell profile induced by that protocol. HKC-immunized mice, which displayed no greater protection than controls, did not have the amplifier cells. Based on our findings, we propose that the protective anticryptococcal T cells are the CD4+ T cells which have been shown to be responsible for DTH reactivity and/or the CD4+ T cells which amplify the DTH response and which have been previously shown to produce high levels of gamma interferon and interleukin 2. Our results imply that there are protective and nonprotective cell-mediated immune responses and highlight the complexity of the immune response to C. neoformans antigens.

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Faculty Opinions recommendation of Regulatory T cells facilitate the nuclear accumulation of inducible cAMP early repressor (ICER) and suppress nuclear factor of activated T cell c1 (NFATc1).

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.10640957.11516056 ◽

2011 ◽

Author(s):

Claire Chougnet

Keyword(s):

T Cells ◽

T Cell ◽

Regulatory T Cells ◽

Nuclear Accumulation ◽

Nuclear Factor ◽

Inducible Camp Early Repressor ◽

Activated T Cell

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A Transcription Function for the T Cell–Specific Adapter (Tsad) Protein in T Cells

Journal of Experimental Medicine ◽

10.1084/jem.193.12.1425 ◽

2001 ◽

Vol 193 (12) ◽

pp. 1425-1430 ◽

Cited By ~ 26

Author(s):

Francesc Marti ◽

Nicholas H. Post ◽

Elena Chan ◽

Philip D. King

Keyword(s):

T Cells ◽

T Cell ◽

Nuclear Import ◽

Regulatory Protein ◽

Interleukin 2 ◽

Cell Receptor ◽

Sh2 Domain ◽

Nuclear Factor ◽

Transcription Activator ◽

Activated T Cells

T cell–specific adapter (TSAd) protein is an Src homology 2 (SH2) domain–containing adapter molecule implicated in T cell receptor for antigen (TCR)-mediated interleukin 2 (IL-2) secretion in T cells. Here, we demonstrate that a substantial fraction of TSAd is found in the T cell nucleus. Nuclear import of TSAd is an active process that depends on TSAd SH2 domain recognition of a phosphotyrosine-containing ligand. Importantly, we show that TSAd can act as a potent transcriptional activator in T cells. Furthermore, the TSAd SH2 domain appears to be essential for this transcription-activating function independent of its role in nuclear import. Biochemical analyses suggest that a single TSAd SH2 domain ligand of 95–100 kD may be involved in these processes. Consistent with a role as a transcription activator, cotransfection of TSAd with an IL-2 promoter–reporter gene construct results in a considerable upregulation of IL-2 promoter activity. Further, we show that this augmentation requires a functional TSAd SH2 domain. However, TSAd does not appear to modulate the activity of the major recognized IL-2 gene transcription factors, nuclear factor κB (NF-κB), nuclear factor of activated T cells (NFAT), or activator protein 1 (AP-1). These findings point to the function of TSAd as a novel transcription-regulatory protein in T cells and illustrate the importance of the TSAd SH2 domain in this role.

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Equivalent functional nuclear factor of activated T cell 1 mRNA and protein expression in cord blood and adult T cells

Transplantation Journal ◽

10.1097/01.tp.0000084308.19565.2b ◽

2003 ◽

Vol 76 (10) ◽

pp. 1526-1528 ◽

Cited By ~ 4

Author(s):

Rose Marie O???Neill ◽

Denis J. Reen

Keyword(s):

T Cells ◽

T Cell ◽

Protein Expression ◽

Cord Blood ◽

Nuclear Factor ◽

Mrna And Protein Expression ◽

Activated T Cell

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Interleukin-7 induces HIV replication in primary naive T cells through a nuclear factor of activated T cell (NFAT)-dependent pathway

Virology ◽

10.1016/j.virol.2006.02.019 ◽

2006 ◽

Vol 350 (2) ◽

pp. 443-452 ◽

Cited By ~ 26

Author(s):

Elizabeth Z. Managlia ◽

Alan Landay ◽

Lena Al-Harthi

Keyword(s):

T Cells ◽

T Cell ◽

Nuclear Factor ◽

Hiv Replication ◽

Naive T Cells ◽

Naïve T Cells ◽

Interleukin 7 ◽

Activated T Cell ◽

Dependent Pathway

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Pomegranate Polyphenols and Extract Inhibit Nuclear Factor of Activated T-Cell Activity and Microglial Activation In Vitro and in a Transgenic Mouse Model of Alzheimer Disease

Journal of Nutrition ◽

10.3945/jn.112.169516 ◽

2013 ◽

Vol 143 (5) ◽

pp. 597-605 ◽

Cited By ~ 61

Author(s):

Lalida Rojanathammanee ◽

Kendra L. Puig ◽

Colin K. Combs

Keyword(s):

T Cell ◽

Alzheimer Disease ◽

Mouse Model ◽

Transgenic Mouse ◽

Microglial Activation ◽

Cell Activity ◽

Transgenic Mouse Model ◽

Nuclear Factor ◽

Activated T Cell

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p21ras and calcineurin synergize to regulate the nuclear factor of activated T cells.

Journal of Experimental Medicine ◽

10.1084/jem.178.5.1517 ◽

1993 ◽

Vol 178 (5) ◽

pp. 1517-1522 ◽

Cited By ~ 100

Author(s):

M Woodrow ◽

N A Clipstone ◽

D Cantrell

Keyword(s):

T Cells ◽

T Cell ◽

T Cell Activation ◽

Protein Tyrosine Kinase ◽

Cell Activation ◽

Interleukin 2 ◽

Cytosolic Calcium ◽

Nuclear Factor ◽

Activated T Cells ◽

Guanine Nucleotide Binding Protein

In T lymphocytes, triggering of the T cell receptor (TCR) induces several signaling cascades which ultimately synergize to induce the activity of the nuclear factor of activated T cells (NFAT), a DNA binding complex critical to the inducibility and T cell specificity of the T cell growth factor interleukin 2. One immediate consequence of T cell activation via the TCR is an increase in cytosolic calcium. Calcium signals are important for NFAT induction, and recent studies have identified calcineurin, a calcium-calmodulin dependent serine-threonine phosphatase, as a prominent component of the calcium signaling pathway in T cells. A second important molecule in TCR signal transduction is the guanine nucleotide binding protein, p21ras, which is coupled to the TCR by a protein tyrosine kinase dependent mechanism. The experiments presented here show that expression by transfection of mutationally activated calcineurin or activated p21ras alone is insufficient for NFAT transactivation. However, coexpression of the activated calcineurin with activated p21ras could mimic TCR signals in NFAT induction. These data identify calcineurin and p21ras as cooperative partners in T cell activation.

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