Cellular and molecular mechanisms for reduced interleukin 4 and interferon-gamma production by neonatal T cells

J Clin Invest. 1991 Jan;87(1):194-202. doi: 10.1172/JCI114970.


The mechanisms by which T lymphocytes acquire the capacity to produce interleukin 4 (IL-4) and other lymphokines during intrathymic and extrathymic development are poorly understood. To gain insight into this process, we determined the capacity of human neonatal and adult T lineage cell populations to produce IL-4 after polyclonal activation. IL-2 and interferon-gamma (IFN-gamma) production were studied in parallel, since their production by neonatal T cells is known to be similar or diminished, respectively, compared to adult T cells. Production of IL-4 by neonatal CD4+ T cells and IFN-gamma by neonatal CD4+ and CD8+ T cells was markedly lower compared with analogous adult cell populations, whereas IL-2 production was similar. Transcription of IL-4, as determined by nuclear run-on assays, and IL-4 mRNA-containing cells, as determined by in situ hybridization, were undetectable in neonatal T cells, whereas both were detectable in adult T cells. IFN-gamma transcription and IFN-gamma mRNA-containing cells were reduced in neonatal T cells compared with adult T cells. Reduced lymphokine production by neonatal T cells correlated with their lack of a CD45R- (putative memory T cell) population; cells with this surface phenotype comprised 30-40% of the adult CD4+ T cells and were highly enriched for IL-4 and IFN-gamma, but not IL-2 production. IL-4, IFN-gamma, and IL-2 mRNA expression by neonatal CD4+CD8- thymocytes was similar to that found in circulating neonatal CD4+ T cells. Taken together, these findings suggest that the extrathymic generation of memory T cells during postnatal life may result in an increased capacity for IL-4 and IFN-gamma gene expression. In addition, IFN-gamma and IL-2 mRNA were significantly more abundant than IL-4 mRNA in activated neonatal CD4+CD8- thymocytes and CD4+ T cells, as well as adult CD4+ CD45R- T cells. Therefore, the capacity of T lineage cells to express the IL-4 gene may be more restricted compared to other lymphokine genes beginning in intrathymic development. This restricted capacity appears to persist during postnatal extrathymic maturation of T cells.

Publication types

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

MeSH terms

  • Adult
  • Antigens, Differentiation / analysis
  • Antigens, Differentiation, T-Lymphocyte / analysis
  • CD4 Antigens / analysis
  • CD8 Antigens
  • Fetal Blood / immunology*
  • Histocompatibility Antigens / analysis
  • Humans
  • Infant, Newborn
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / genetics
  • Interleukin-2 / genetics
  • Interleukin-4 / biosynthesis*
  • Interleukin-4 / genetics
  • Leukocyte Common Antigens
  • RNA, Messenger / analysis
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Transcription, Genetic


  • Antigens, Differentiation
  • Antigens, Differentiation, T-Lymphocyte
  • CD4 Antigens
  • CD8 Antigens
  • Histocompatibility Antigens
  • Interleukin-2
  • RNA, Messenger
  • Interleukin-4
  • Interferon-gamma
  • Leukocyte Common Antigens