The expression and regulation of a potential lymphokine gene (TCA3) in CD4 and CD8 T cell clones.
The TCA3 gene was originally isolated from a cDNA library derived from a TH1 (inflammatory) T cell clone. Expression of TCA3 RNA was limited to cells in the activated state. Based on its expression profile and the existence of a hydrophobic leader sequence with a predicted cleavage site, we proposed that TCA3 encodes a new lymphokine. In the present study, we examine the subset distribution, kinetics, and regulation of TCA3 RNA expression. We show that TCA3 is expressed in response to selected T cell-activating stimuli. TCA3 is transcribed to peak steady state levels by 4 h after stimulation in TH1, TH2 (helper), and CTL clones. Two intracellular signals, supplied in vitro by phorbol ester and one of several agents capable of increasing intracellular free calcium concentrations, are required for the initiation of TCA3 transcription. In addition, TCA3 transcription is blocked by anti-L3T4 mAb, suggesting that prior signaling through L3T4 can inhibit expression of TCA3 and other lymphokines. In contrast to IL-2, IL-4, and IFN-gamma TCA3 is uniformly expressed at high levels among all individual T cell clones examined, including four TH1, three TH2, and three CTL clones. Furthermore, activation-specific TCA3 expression can be dissociated from T cell proliferation.
Wilson
S D
SD
Department of Pathology, Harvard Medical School, Boston, MA 02115.
Burd
P R
PR
Billings
P R
PR
Martin
C A
CA
Dorf
M E
ME
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001667:Binding, Competitive; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism; D003115:Colony-Stimulating Factors / Q000235:genetics; D005786:Gene Expression Regulation; D005796:Genes; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000235:genetics; D007377:Interleukin-3 / Q000235:genetics; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010641:Phenotype; D012313:RNA / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007377:Interleukin-3; D008222:Lymphokines; C051344:t cell-activating lymphokine; D012313:RNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor