Biomedical subjects

H E Liang

Publications and source records attributed to H E Liang.

5 recordsLinked to original sources

PubMed1997

CD28-costimulation activates cyclic AMP-responsive element-binding protein in T lymphocytes.

Cyclic AMP-responsive element binding protein (CREB) mediates gene expression in response to cAMP stimulation. The transcriptional activity of CREB depends on both the phosphorylation of Ser133 and the recruitment of cofactor for assembly of transcriptional complex. Extensive Ser133 phosphorylation of CREB was induced during T cell activation. This phosphorylation event is essential for IL-2 gene expression. However, phosphorylation of CREB at Ser133 was not sufficient for transcriptional activity by CREB. The presence of a second signal from CD28, a potent costimulatory molecule on T cells, stimulated CREB-mediated gene expression. CD28, an effective costimulator of T cell activation and IL-2 gene expression, is shown to induce CREB activation in the presence of anti-CD3 or O-tetradecanoylphorbol 13-acetate. These two signals together stimulated a CRE-dependent reporter gene, the proliferating cell nuclear Ag promoter, and transactivation by the GAL4-CREB fusion protein. Thus optimal induction of CREB, similar to the full activation of T lymphocytes, may be mediated by two distinct signal transductions. Using the specific kinase inhibitor, one of the two pathways appeared to involve mitogen-activated protein kinase kinase but not protein kinase C, protein kinase A, or p70 S6 kinase.

Activating Transcription Factor 1↗

PubMed1996

Different V beta usage in antigen-specific and alloreactive T cells specific for the same MHC elements.

V beta 8 has been shown to be used in the majority of antigen specific T cell hybridomas restricted by I-Ad and I-Ed. The usage of V beta 8 in these T cell responses in vivo was confirmed as V beta 8 depleted BALB/c mice responded weakly to these I-Ad- and I-Ed-restricted antigens. We used this deletion assay to further examine if V beta 8 is similarly dominantly used in alloreactive T cell specific for I-Ad/Ed. The depletion of V beta 8-population in allogenic mice did not affect the alloreactive responses toward I-Ad/Ed. Although specific for the same MHC, there is no apparent overlap on the use of TCR V beta 8 between alloreactive T cells and antigen-specific T cells.

Amino Acid Sequence↗

PubMed1995

Limited regulatory effect of T cell receptor-derived peptides.

T cell receptor (TCR)-derived peptides have been used to induce regulatory T cells which recognize T cells of specific elements and downregulate the autoimmune response. Consistent with these observations, priming of peptides corresponding to V beta 8 complementarity-determining region 2 (CDR2) was found to specifically suppress the proliferation of V beta 8+ T cells in the draining lymph nodes. Similarly, the generation of V beta 8-dominant T cell responses was prevented locally by vaccination with V beta 8 CDR2 peptides. There was a good correlation between the downregulation of V beta 8+ T cells and the inhibition of the corresponding T cell responses in different lymphoid tissues. No systemic inhibition could be detected even after an interval which would allow the redistribution of the "regulatory T cells." T cells specific for V beta 8 CDR2 peptides was generated following peptide immunization. However, the appearance of these TCR peptide-specific T cells was independent of the downregulation of V beta 8+ T cells. The transient and localized inhibitory effects of TCR-derived peptides indicate that these peptides have very limited use in regulating specific T cell response.

Amino Acid Sequence↗

PubMed1994

Flexibility of the T cell receptor repertoire.

Alternative T cell receptor (TcR) gene usage between mice of different Mls alleles has been demonstrated in a number of T cell responses. A clear illustration of a flexible TcR V beta usage in the same strain of mice remains to be established. Using a model system in which I-Ek-restricted T cells recognizing lambda repressor cI protein (cI) 12-26 and pigeon cytochrome c (pcc) 81-104 predominantly use V beta 3 in B10.A and B10.BR mice, and V beta 1 in Mls-2a-bearing A/J and C3H mice, we have first demonstrated that the hierarchy of TcR V beta usage can not be inferred from one strain of mice to the other. The presumed flexibility of V beta 3 to V beta 1 did not exist in B10.BR mice in the given responses. Instead, a switch of dominant TcR from V beta 1/V beta 3 to V beta 8 was identified in C3H and B10.BR mice. In contrast, there was an absolute rigidity in TcR repertoire usage in some mouse strains such as A/J. The lack of flexibility was not due to slow generating kinetics of replacing T cells; since A/J mice treated with staphylococcal enterotoxin A from birth on still responded poorly to cI 12-26 and pcc 81-104. Therefore, whether TcR V beta usage in a T cell response would be flexible or rigid is highly dependent on each strain of mice. However, even the plasticity seen in B10.BR mice is very limited and further tolerance of the V beta 8+ population results in non-responsiveness toward the given antigens.

Amino Acid Sequence↗

PubMedDate not supplied

Atypical signaling defects prevent IL-2 gene expression in lpr/lpr CD4-CD8- cells.

T cells with CD4-CD8- (double negative, DN) phenotype in MRL-lpr/lpr mouse serve as a model to establish the correlation between the extremely low IL-2 gene expression and the specific signaling inactivation. The extent of nonresponsiveness in lpr DN cells was distinctive in several unusual defects. First, the poor IL-2 production in lpr DN cells could not be restored by supplement of signals known to augment IL-2 response in normal T cells. Second, the activations of both mitogen-activated protein (MAP) kinase and c-Jun N-terminal kinase (JNK) were attenuated in lpr DN cells upon direct activation by TPA/A23187. Third, IL-2 mRNA was degraded much faster in lpr DN cells than that in normal T cells. Fourth, of the four major transcriptional elements on IL-2 promoter, only AP-1 and nuclear factor of activated T cells (NFAT)-binding activities were suppressed in lpr DN T cells. Altogether, these results suggest that an extremely low level of IL-2 production in lpr DN T cells was due to both the increased instability of mRNA and the reduced activation of IL-2 gene promoter, the latter defect could be attributed to the inactivation of AP-1 and NF-AT as well as the poor activation of the upstream MAP kinase and JNK.

Animals↗