2784764

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Studies of cloned CD4+ T cell lines have shown that they can be separated into two distinct subsets with distinctions in their functional capabilities and by the differential release of either interleukin 2 (IL 2) (TH1/inflammatory type) or IL 4 (TH2/helper type) upon activation. To establish if in vivo-derived CD4+ T cells can exhibit distinct subsets we have investigated whether normal CD4+ T cells demonstrate differential expression of IL 2 and IL 4 mRNA, and secretion of IL 2 and IL 4 after primary stimulation in vitro. Utilizing the technique of in situ hybridization IL 2 and IL 4 gene expression in individual CD4+ T cells was readily detectable after concanavalin A (Con A) phytohemagglutinin (PHA) or pokeweed mitogen (PWM)-mediated activation. The frequencies of activated T cells producing IL 2 and IL 4 mRNA after Con A or PHA activation were approximately equivalent (30-40% of cells); however, after PWM activation the number of CD4+ T cells expressing IL 4 mRNA (78%) was more than twofold greater than the number of cells producing IL 2 mRNA (30%). Maximal levels of IL 2 gene expression occurred 24 h after mitogen activation whereas the highest levels of IL 4 mRNA were not detected until 48 h after mitogen activation. Similar distinctions in the kinetics of IL 2 and IL 4 secretion after mitogen activation were also found demonstrating good concordance in the observed expression of IL 2 and IL 4 mRNA and the levels of secreted lymphokines detected by bioassay. Most importantly, we have shown by in situ hybridization analysis that the majority of individual CD4+ T cells produce only IL 2 or IL 4 mRNA, and not both, after primary activation in vitro. By contrast, most CD4+ T cells activated in the presence of PMA and ionophore express both IL 2 and IL 4 mRNA. Our studies demonstrate that in normal, non-clonal populations of CD4+ T cells, the production of IL 2 and IL 4 is independently regulated in the majority of cells and appears to be stimulus dependent.

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0014-2980

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231-8

pubmed-meshheading:2784764-Animals, pubmed-meshheading:2784764-Antigens, Differentiation, T-Lymphocyte, pubmed-meshheading:2784764-Clone Cells, pubmed-meshheading:2784764-Gene Expression Regulation, pubmed-meshheading:2784764-Interleukin-2, pubmed-meshheading:2784764-Interleukin-4, pubmed-meshheading:2784764-Interleukins, pubmed-meshheading:2784764-Ionophores, pubmed-meshheading:2784764-Kinetics, pubmed-meshheading:2784764-Lymphocyte Activation, pubmed-meshheading:2784764-Lymphokines, pubmed-meshheading:2784764-Mice, pubmed-meshheading:2784764-Mice, Inbred BALB C, pubmed-meshheading:2784764-Phenotype, pubmed-meshheading:2784764-RNA, Messenger, pubmed-meshheading:2784764-Receptors, Immunologic, pubmed-meshheading:2784764-T-Lymphocytes, pubmed-meshheading:2784764-Tetradecanoylphorbol Acetate

Differential activation of cytokine genes in normal CD4-bearing T cells is stimulus dependent.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't