Stimulatory and costimulatory effects of IL-18 directed to different small intestinal CD43 T cell subsets.
This study has examined the stimulatory and costimulatory effects of IL-18 on two subsets of murine small intestinal intraepithelial lymphocytes (IELs) defined by the expression of the CD43 S7 glycoform. Data from gene array studies and real-time PCR indicated that S7(+) IELs had significantly higher levels of gene expression for the IL-18 receptor and the IL-18R accessory protein than S7(-) IELs. IL-18 costimulation of IELs in conjunction with CD3-induced activation resulted in significantly greater proliferation than CD3 stimulation alone. In CFSE dilution experiments, IL-18 costimulation favored the S7(+) IEL population. IL-18 costimulation did not affect apoptosis of either S7(-) or S7(+) IELs compared with CD3 stimulation alone. Although IL-18 costimulation did not alter the total number of IFN-gamma-producing cells relative to CD3 stimulation alone, twice as many S7(+) IELs were IFN-gamma -secreting cells than S7(-) IELs in both CD3-stimulated and IL-18-costimulated cultures. Notably, direct IL-18 stimulation in the absence of CD3 activation induced an IFN-gamma response that was predominantly directed to the S7(+) population, indicating that IL-18 is itself an IFN-gamma activational signal for intestinal T cells. In contrast, direct IL-18 stimulation of IELs did not generate TNF-alpha-producing cells, indicating a differential response in the activation of proinflammatory cytokines following IL-18 exposure. These findings point to distinctly different activational effects of IL-18 on IELs, both with regard to the type of functional responses elicited and with respect to the IEL subsets affected.
Montufar-Solis
Dina
D
Department of Diagnostic Sciences, University of Texas Health Science Center at Houston, Dental Branch, Houston, TX 77030, USA.
Wang
Heuy-Ching
HC
Klein
John R
JR
D000818:Animals; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016923:Cell Death / Q000276:immunology; D049109:Cell Proliferation; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000378:metabolism; D020382:Interleukin-18 / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D007421:Intestine, Small / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051917:Leukosialin / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D053724:Receptors, Interleukin-18 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
D017252:CD3 Complex; D020382:Interleukin-18; D051917:Leukosialin; D053724:Receptors, Interleukin-18; D007371:Interferon-gamma
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