Pro-interleukin-1 beta production by a subpopulation of human T cells, but not NK cells, in response to interleukin-2.
Previous studies have shown that IL-2-stimulated peripheral blood mononuclear cells (PBMC) produce IL-1 beta and TNF alpha and that monocytes are the primary source of these IL-2-inducible cytokines. In this report, we provide evidence that monocytes are not the only source. We examined cytokine production by IL-2-treated, nonmonocytic PBMC and found that a population of nonadherent low-density cells (NLDC) produced both IL-1 beta and TNF alpha in response to IL-2. IL-1 beta was synthesized by IL-2-treated NLDC as the 35-kDa intracellular precursor (pro-IL-1 beta), but was neither secreted nor processed to the mature 17-kDa form of the molecule. To determine which cells within the NLDC population generated pro-IL-1 beta and TNF alpha in response to IL-2, we positively selected NK cells and T cells, the two major components of NLDC, using specific monoclonal antibodies. Although IL-2-treated CD16+ NK cells produced TNF alpha and transcribed IL-1 beta mRNA, they did not synthesize the IL-1 beta protein. Conversely, LPS-treated CD16+ and IL-2-treated CD4+ and CD5+ NLDC produced elevated levels of both TNF alpha and IL-1 beta. Our findings illustrate the complex nature of IL-1 beta production by IL-2-stimulated PBMC and suggest that the factors controlling IL-1 beta gene transcription and translation, as well as secretion and processing, vary widely as a function of cell type and stimulus.
Numerof
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Immunology Program, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachusetts.
Kotik
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Dinarello
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CA
Mier
J W
JW
D015703:Antigens, CD / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis; D015152:Blotting, Northern; D015153:Blotting, Western; D002469:Cell Separation; D002499:Centrifugation, Density Gradient; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D007376:Interleukin-2 / Q000494:pharmacology*; D007526:Isoelectric Point; D007694:Killer Cells, Natural / Q000502:physiology*; D011498:Protein Precursors / Q000096:biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D011961:Receptors, Fc / Q000032:analysis; D017452:Receptors, IgG; D013601:T-Lymphocytes / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D007375:Interleukin-1; D007376:Interleukin-2; D011498:Protein Precursors; D012333:RNA, Messenger; D011961:Receptors, Fc; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha