Complexity of the primary genetic response to mitogenic activation of human T cells.

Abstract

We describe the isolation and characterization of more than 60 novel cDNA clones that constitute part of the immediate genetic response to resting human peripheral blood T cells after mitogen activation. This primary response was highly complex, both in the absolute number of inducible genes and in the diversity of regulation. Although most of the genes expressed in activated T cells were shared with the activation response of normal human fibroblasts, a significant number were more restricted in tissue specificity and thus likely encode or effect the differentiated functions of activated T cells. The activatable genes could be further differentiated on the basis of kinetics of induction, response to cycloheximide, and sensitivity to the immunosuppressive drug cyclosporin A. It is of note that cyclosporin A inhibited the expression of more than 10 inducible genes, which suggests that this drug has a broad genetic mechanism of action.

Gem: an Induced, Immediate Early Protein Belonging to the Ras Family

“…Deregulated expression of Gem reduced the number of selectable colonies to <0.1% of that obtained with cells transfected with the vector alone (16). Similarly, the number of selectable colonies obtained after cotransfection of 3T3 cells with pMT2T-GEM and pSV2-neo was -20% of that obtained after transfection with pSV2-neo alone (2 number of circulating CD4+ T lymphocytes (1). Recently, it has been shown in both mice and humans that CD4+ T cells represent a functionally heterogeneous population in their profile of cytokine production (2).…”

“…We have cloned mitogen-induced genes from human peripheral blood T cells on the basis of differential expression of mRNA between resting and stimulated cells (1). One such clone, pAT 270, is now shown to encode a protein we have termed Gem because it binds GTP and is induced by mitogens.…”

Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor.

“…DISCUSSION Activation of peripheral blood lymphocytes by lectins such as phytohemagglutinin and pokeweed mitogen induces the expression of a number of known and unknown cytokine genes (33). We are in the process of isolating and characterizing the novel cytokine-like molecules by using multiple approaches.…”

“…Most cytokine genes have been shown to be induced by lectins and superinduced by cycloheximide (33). In addition, the presence of destabilizing sequences such as TATT on the 3' untranslated region of the clones, a salient feature of cytokine messages (28), was also taken into consideration.…”

The EWS/TEC fusion protein encoded by the t(9;22) chromosomal translocation in human chondrosarcomas is a highly potent transcriptional activator

“…Induction of NGFI-B correlates with di erentiation of rat PC12 cells into neuronal cells upon treatment with nerve growth factor (Milbrandt, 1988). NURR1 expression is rapidly induced in the regenerating rat liver following partial hepatectomy (Scearce et al, 1993), as is the expression of TEC in phorbol 12-myristate 13-acetate (PMA) activated human T cells (Zipfel et al, 1989, in this last reference TEC is referred to as clone pAT229). The DNAbinding domain of these three receptors are almost identical, those of TEC and NURR1 sharing 98% identity, while those of TEC and NGFI-B share 91% identity.…”