Abstract
Cytokines are important mediators involved in the development of effector cells and in the regulation of immune responses. The gene expression of these mediators in T cell subset has yet to be fully elucidated. Using sensitive reverse transcription-polymerase chain reaction (RT-PCR), the kinetics of cytokine gene expression in human CD4+ and CD8+ T cells were examined. CD4+ T cells were more readily activated by phorbol myristate acetate (PMA) and phytohaemagglutinin (PHA) than CD8+ T cells in terms of the IL-2 receptor (IL-2R) mRNA expression. Quantitative differences in cytokine gene expression between CD4+ and CD8+ T cells were confirmed and higher levels of cytokine mRNAs were induced in CD4+ than in CD8+ T cells. Early induction of IL-2 mRNA was observed in both T cell subsets. The demonstration of different kinetics of cytokine gene expression illustrates one of the examples of the complexity of immunoregulation. The differential response of cytokine gene expression in different T cell subsets should be taken into consideration when clinical studies in cytokine production by peripheral blood mononuclear cells are interpreted.
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- Brenner C. A., Tam A. W., Nelson P. A., Engleman E. G., Suzuki N., Fry K. E., Larrick J. W. Message amplification phenotyping (MAPPing): a technique to simultaneously measure multiple mRNAs from small numbers of cells. Biotechniques. 1989 Nov-Dec;7(10):1096–1103. [PubMed] [Google Scholar]
- Carter B. Z., Malter J. S. Regulation of mRNA stability and its relevance to disease. Lab Invest. 1991 Dec;65(6):610–621. [PubMed] [Google Scholar]
- Coles M., Rose M., Yacoub M. Appearance of cells bearing the interleukin-2 receptor in peripheral blood of cardiac transplant patients and their correlation with rejection episodes. Transplant Proc. 1987 Feb;19(1 Pt 3):2546–2547. [PubMed] [Google Scholar]
- Corrigan C. J., Kay A. B. CD4 T-lymphocyte activation in acute severe asthma. Relationship to disease severity and atopic status. Am Rev Respir Dis. 1990 Apr;141(4 Pt 1):970–977. doi: 10.1164/ajrccm/141.4_Pt_1.. [DOI] [PubMed] [Google Scholar]
- Gajewski T. F., Schell S. R., Nau G., Fitch F. W. Regulation of T-cell activation: differences among T-cell subsets. Immunol Rev. 1989 Oct;111:79–110. doi: 10.1111/j.1600-065x.1989.tb00543.x. [DOI] [PubMed] [Google Scholar]
- Gauchat J. F., Walker C., De Weck A. L., Stadler B. M. Stimulation-dependent lymphokine mRNA levels in human mononuclear cells. Eur J Immunol. 1988 Sep;18(9):1441–1446. doi: 10.1002/eji.1830180921. [DOI] [PubMed] [Google Scholar]
- Gilliland G., Perrin S., Blanchard K., Bunn H. F. Analysis of cytokine mRNA and DNA: detection and quantitation by competitive polymerase chain reaction. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2725–2729. doi: 10.1073/pnas.87.7.2725. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kelso A., Glasebrook A. L. Secretion of interleukin 2, macrophage-activating factor, interferon, and colony-stimulating factor by alloreactive T lymphocyte clones. J Immunol. 1984 Jun;132(6):2924–2931. [PubMed] [Google Scholar]
- Kelso A., Troutt A. B., Maraskovsky E., Gough N. M., Morris L., Pech M. H., Thomson J. A. Heterogeneity in lymphokine profiles of CD4+ and CD8+ T cells and clones activated in vivo and in vitro. Immunol Rev. 1991 Oct;123:85–114. doi: 10.1111/j.1600-065x.1991.tb00607.x. [DOI] [PubMed] [Google Scholar]
- Kim T., Kanayama Y., Negoro N., Okamura M., Takeda T., Inoue T. Serum levels of interferons in patients with systemic lupus erythematosus. Clin Exp Immunol. 1987 Dec;70(3):562–569. [PMC free article] [PubMed] [Google Scholar]
- Lai K. N., Leung J. C., Lai F. M., Tam J. S. T-lymphocyte activation in IgA nephropathy: serum-soluble interleukin 2 receptor level, interleukin 2 production, and interleukin 2 receptor expression by cultured lymphocytes. J Clin Immunol. 1989 Nov;9(6):485–492. doi: 10.1007/BF00918018. [DOI] [PubMed] [Google Scholar]
- Lai K. N., Leung J. C., Li P. K., Lui S. F. Cytokine production by peripheral blood mononuclear cells in IgA nephropathy. Clin Exp Immunol. 1991 Aug;85(2):240–245. doi: 10.1111/j.1365-2249.1991.tb05712.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mosmann T. R., Coffman R. L. Heterogeneity of cytokine secretion patterns and functions of helper T cells. Adv Immunol. 1989;46:111–147. doi: 10.1016/s0065-2776(08)60652-5. [DOI] [PubMed] [Google Scholar]
- Paliard X., de Waal Malefijt R., Yssel H., Blanchard D., Chrétien I., Abrams J., de Vries J., Spits H. Simultaneous production of IL-2, IL-4, and IFN-gamma by activated human CD4+ and CD8+ T cell clones. J Immunol. 1988 Aug 1;141(3):849–855. [PubMed] [Google Scholar]
- Rappolee D. A., Wang A., Mark D., Werb Z. Novel method for studying mRNA phenotypes in single or small numbers of cells. J Cell Biochem. 1989 Jan;39(1):1–11. doi: 10.1002/jcb.240390102. [DOI] [PubMed] [Google Scholar]
- Rappolee D. A., Werb Z. mRNA phenotyping for studying gene expression in small numbers of cells: platelet-derived growth factor and other growth factors in wound-derived macrophages. Am J Respir Cell Mol Biol. 1990 Jan;2(1):3–10. doi: 10.1165/ajrcmb/2.1.3. [DOI] [PubMed] [Google Scholar]
- Salgame P., Abrams J. S., Clayberger C., Goldstein H., Convit J., Modlin R. L., Bloom B. R. Differing lymphokine profiles of functional subsets of human CD4 and CD8 T cell clones. Science. 1991 Oct 11;254(5029):279–282. doi: 10.1126/science.254.5029.279. [DOI] [PubMed] [Google Scholar]
- Sander B., Andersson J., Andersson U. Assessment of cytokines by immunofluorescence and the paraformaldehyde-saponin procedure. Immunol Rev. 1991 Feb;119:65–93. doi: 10.1111/j.1600-065x.1991.tb00578.x. [DOI] [PubMed] [Google Scholar]
- Sanderson C. J., Strath M., Warren D. J., O'Garra A., Kirkwood T. B. The production of lymphokines by primary alloreactive T-cell clones: a co-ordinate analysis of 233 clones in seven lymphokine assays. Immunology. 1985 Dec;56(4):575–584. [PMC free article] [PubMed] [Google Scholar]
- Scott P., Kaufmann S. H. The role of T-cell subsets and cytokines in the regulation of infection. Immunol Today. 1991 Oct;12(10):346–348. doi: 10.1016/0167-5699(91)90063-Y. [DOI] [PubMed] [Google Scholar]
- Semenzato G., Bambara L. M., Biasi D., Frigo A., Vinante F., Zuppini B., Trentin L., Feruglio C., Chilosi M., Pizzolo G. Increased serum levels of soluble interleukin-2 receptor in patients with systemic lupus erythematosus and rheumatoid arthritis. J Clin Immunol. 1988 Nov;8(6):447–452. doi: 10.1007/BF00916949. [DOI] [PubMed] [Google Scholar]
- Staynov D. Z., Lee T. H. Expression of interleukin-5 and granulocyte-macrophage colony-stimulating factor in human peripheral blood mononuclear cells after activation with phorbol myristate acetate. Immunology. 1992 Jan;75(1):196–201. [PMC free article] [PubMed] [Google Scholar]
- Street N. E., Mosmann T. R. Functional diversity of T lymphocytes due to secretion of different cytokine patterns. FASEB J. 1991 Feb;5(2):171–177. doi: 10.1096/fasebj.5.2.1825981. [DOI] [PubMed] [Google Scholar]
- Umetsu D. T., Jabara H. H., DeKruyff R. H., Abbas A. K., Abrams J. S., Geha R. S. Functional heterogeneity among human inducer T cell clones. J Immunol. 1988 Jun 15;140(12):4211–4216. [PubMed] [Google Scholar]
- Vilcek J., Henriksen-Destefano D., Siegel D., Klion A., Robb R. J., Le J. Regulation of IFN-gamma induction in human peripheral blood cells by exogenous and endogenously produced interleukin 2. J Immunol. 1985 Sep;135(3):1851–1856. [PubMed] [Google Scholar]
- Wang A. M., Doyle M. V., Mark D. F. Quantitation of mRNA by the polymerase chain reaction. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9717–9721. doi: 10.1073/pnas.86.24.9717. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wejstål R., Norkrans G., Weiland O., Schvarcz R., Fuchs D., Wachter H., Fryden A., Glaumann H. Lymphocyte subsets and beta 2-microglobulin expression in chronic hepatitis C/non-A, non-B. Effects of interferon-alpha treatment. Clin Exp Immunol. 1992 Mar;87(3):340–345. doi: 10.1111/j.1365-2249.1992.tb02999.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wesselingh S. L., Gough N. M., Finlay-Jones J. J., McDonald P. J. Detection of cytokine mRNA in astrocyte cultures using the polymerase chain reaction. Lymphokine Res. 1990 Summer;9(2):177–185. [PubMed] [Google Scholar]