CELLULAR AND MOLECULAR MECHANISMS FOR REDUCED INTERLEUKIN-4 AND INTERFERON-GAMMA PRODUCTION BY NEONATAL T-CELLS

被引:224
作者
LEWIS, DB [1 ]
YU, CC [1 ]
MEYER, J [1 ]
ENGLISH, BK [1 ]
KAHN, SJ [1 ]
WILSON, CB [1 ]
机构
[1] UNIV WASHINGTON, DEPT IMMUNOL, DIV INFECT DIS, SEATTLE, WA 98195 USA
关键词
CD45; INTERFERON-GAMMA; INTERLEUKIN-4; MEMORY T-CELLS; NEONATAL T-CELLS;
D O I
10.1172/JCI114970
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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. INF-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.
引用
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页码:194 / 202
页数:9
相关论文
共 75 条
[1]  
AKBAR AN, 1988, J IMMUNOL, V140, P2171
[2]   DEFICIENCY OF IMMUNE INTERFERON-PRODUCTION BY LEUKOCYTES OF NORMAL NEWBORNS [J].
BRYSON, YJ ;
WINTER, HS ;
GARD, SE ;
FISCHER, TJ ;
STIEHM, ER .
CELLULAR IMMUNOLOGY, 1980, 55 (01) :191-200
[3]  
BUDD RC, 1987, J IMMUNOL, V138, P1009
[4]  
BUDD RC, 1987, J IMMUNOL, V138, P3583
[5]  
BUDD RC, 1987, J IMMUNOL, V138, P3120
[6]  
BURCHETT SK, 1988, J IMMUNOL, V140, P3473
[7]   USE OF MONOCLONAL-ANTIBODIES AS SENSITIVE AND SPECIFIC PROBES FOR BIOLOGICALLY-ACTIVE HUMAN GAMMA-INTERFERON [J].
CHANG, TW ;
MCKINNEY, S ;
LIU, V ;
KUNG, PC ;
VILCEK, J ;
LE, JM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1984, 81 (16) :5219-5222
[8]   2 TYPES OF MOUSE HELPER T-CELL CLONE .3. FURTHER DIFFERENCES IN LYMPHOKINE SYNTHESIS BETWEEN TH1 AND TH2 CLONES REVEALED BY RNA HYBRIDIZATION, FUNCTIONALLY MONOSPECIFIC BIOASSAYS, AND MONOCLONAL-ANTIBODIES [J].
CHERWINSKI, HM ;
SCHUMACHER, JH ;
BROWN, KD ;
MOSMANN, TR .
JOURNAL OF EXPERIMENTAL MEDICINE, 1987, 166 (05) :1229-1244
[9]  
CHILMONCZYK BA, 1985, J IMMUNOL, V134, P4184
[10]  
CLEMENT LT, 1988, J IMMUNOL, V141, P1464