Tags

Type your tag names separated by a space and hit enter

Immunomodulatory effects of transforming growth factor-beta on T lymphocytes. Induction of CD8 expression in the CTLL-2 cell line and in normal thymocytes.
J Immunol. 1992 Jun 15; 148(12):3847-56.JI

Abstract

We investigated the role of transforming growth factor-beta 1 (TGF-beta) in regulation of T cell growth and differentiation. Treatment of CTLL-2 cells with TGF-beta inhibited IL-2-dependent proliferation and caused morphologic changes as well as increased adherence. A major change of phenotype in TGF-beta-treated cells was the de novo expression of CD8 alpha chain in 35% of cells, which required the continuous presence of TGF-beta. Of the CD8 alpha+ cells, 20 to 30% co-expressed CD8 beta chain. Increased CD8 expression occurred even in the total absence of cell growth, was not a consequence of growth inhibition, and was not a result of selective growth or survival of CD8+ cells. New RNA synthesis was required for TGF beta-induced CD8 alpha surface expression, inasmuch as this was prevented by treatment with actinomycin D. Northern blot analysis demonstrated that cells treated with IL-2 + TGF-beta rapidly accumulated mRNA encoding both chains of the CD8 dimer, to a level fourfold greater than control by 6 to 12 h. In contrast, the IL-2-dependent increases in IL-2R alpha, IL-2R beta, and Granzyme B mRNA levels in these cultures were profoundly inhibited by TGF-beta. When unfractionated murine thymocytes were stimulated with phorbol dibutyrate plus ionomycin and cultured with IL-2 + TGF-beta, an increase in CD8 alpha mRNA was seen and greater numbers of CD8+ cells with higher levels of CD8 alpha and CD8 beta surface expression resulted, as compared to controls treated with IL-2 alone. Furthermore, similar treatment of CD4-CD8-(double negative) thymocytes with TGF-beta induced de novo CD8 alpha expression by a substantial number of cells, and the majority of these CD8+ cells lacked TCR/CD3. These data suggest that TGF-beta has both positive and negative regulatory effects on the expression of gene products important for T lymphocyte differentiation and function.

Authors+Show Affiliations

Department of Microbiology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

1602133

Citation

Inge, T H., et al. "Immunomodulatory Effects of Transforming Growth Factor-beta On T Lymphocytes. Induction of CD8 Expression in the CTLL-2 Cell Line and in Normal Thymocytes." Journal of Immunology (Baltimore, Md. : 1950), vol. 148, no. 12, 1992, pp. 3847-56.
Inge TH, McCoy KM, Susskind BM, et al. Immunomodulatory effects of transforming growth factor-beta on T lymphocytes. Induction of CD8 expression in the CTLL-2 cell line and in normal thymocytes. J Immunol. 1992;148(12):3847-56.
Inge, T. H., McCoy, K. M., Susskind, B. M., Barrett, S. K., Zhao, G., & Bear, H. D. (1992). Immunomodulatory effects of transforming growth factor-beta on T lymphocytes. Induction of CD8 expression in the CTLL-2 cell line and in normal thymocytes. Journal of Immunology (Baltimore, Md. : 1950), 148(12), 3847-56.
Inge TH, et al. Immunomodulatory Effects of Transforming Growth Factor-beta On T Lymphocytes. Induction of CD8 Expression in the CTLL-2 Cell Line and in Normal Thymocytes. J Immunol. 1992 Jun 15;148(12):3847-56. PubMed PMID: 1602133.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immunomodulatory effects of transforming growth factor-beta on T lymphocytes. Induction of CD8 expression in the CTLL-2 cell line and in normal thymocytes. AU - Inge,T H, AU - McCoy,K M, AU - Susskind,B M, AU - Barrett,S K, AU - Zhao,G, AU - Bear,H D, PY - 1992/6/15/pubmed PY - 1992/6/15/medline PY - 1992/6/15/entrez SP - 3847 EP - 56 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 148 IS - 12 N2 - We investigated the role of transforming growth factor-beta 1 (TGF-beta) in regulation of T cell growth and differentiation. Treatment of CTLL-2 cells with TGF-beta inhibited IL-2-dependent proliferation and caused morphologic changes as well as increased adherence. A major change of phenotype in TGF-beta-treated cells was the de novo expression of CD8 alpha chain in 35% of cells, which required the continuous presence of TGF-beta. Of the CD8 alpha+ cells, 20 to 30% co-expressed CD8 beta chain. Increased CD8 expression occurred even in the total absence of cell growth, was not a consequence of growth inhibition, and was not a result of selective growth or survival of CD8+ cells. New RNA synthesis was required for TGF beta-induced CD8 alpha surface expression, inasmuch as this was prevented by treatment with actinomycin D. Northern blot analysis demonstrated that cells treated with IL-2 + TGF-beta rapidly accumulated mRNA encoding both chains of the CD8 dimer, to a level fourfold greater than control by 6 to 12 h. In contrast, the IL-2-dependent increases in IL-2R alpha, IL-2R beta, and Granzyme B mRNA levels in these cultures were profoundly inhibited by TGF-beta. When unfractionated murine thymocytes were stimulated with phorbol dibutyrate plus ionomycin and cultured with IL-2 + TGF-beta, an increase in CD8 alpha mRNA was seen and greater numbers of CD8+ cells with higher levels of CD8 alpha and CD8 beta surface expression resulted, as compared to controls treated with IL-2 alone. Furthermore, similar treatment of CD4-CD8-(double negative) thymocytes with TGF-beta induced de novo CD8 alpha expression by a substantial number of cells, and the majority of these CD8+ cells lacked TCR/CD3. These data suggest that TGF-beta has both positive and negative regulatory effects on the expression of gene products important for T lymphocyte differentiation and function. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/1602133/Immunomodulatory_effects_of_transforming_growth_factor_beta_on_T_lymphocytes__Induction_of_CD8_expression_in_the_CTLL_2_cell_line_and_in_normal_thymocytes_ L2 - https://www.jimmunol.org/lookup/pmidlookup?view=long&pmid=1602133 DB - PRIME DP - Unbound Medicine ER -