Maximum immunobioactivity of murine small intestinal intraepithelial lymphocytes resides in a subpopulation of CD43+ T cells.
CD43 has been linked to many function-associated T cell activities. Using mAbs that recognize two different CD43 determinants, we show that, although mouse small intestinal intraepithelial lymphocytes (IELs) expressed the CD43 core molecule reactive with mAb R2/60, only about one-half of the total IELs-including some but not all of the TCRalphabeta and TCRgammadelta cells-expressed the CD43 S7(-) reactive determinant. CD43 S7(+) IELs secreted more IL-2, IL-4, IL-10, IL-17, and IFN-gamma following anti-CD3 stimulation, and were >4-fold more cytotoxic in fresh isolates and >16-fold more cytotoxic after anti-CD3 stimulation, than S7(-) IELs. S7(+) but not S7(-) IELs from the ileum of IL-10(-/-) mice spontaneously produced IFN-gamma. In vivo BrdU uptake by IELs in non-Ag-primed mice was greatest in the S7(+) population, indicating that significantly more S7(+) IELs than S7(-) IELs undergo cell expansion under normal homeostatic conditions. DNA microarray analyses showed that S7(+) IELs expressed higher levels of genes associated with activated T cells, whereas S7(-) IELs expressed genes used in the regulation of NK cells. These findings define two functionally distinct populations of IELs based on CD43 expression independent of TCR class, and they identify a subset of IELs that may serve as a target to better control intestinal inflammation.
Wang
Heuy-Ching
HC
Department of Diagnostic Sciences, Dental Branch, University of Texas Health Science Center at Houston, 6516 M.D. Anderson Boulevard, Houston, TX 77030, USA.
Montufar-Solis
Dina
D
Teng
Ba-Bie
BB
Klein
John R
JR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000378:metabolism; D015703:Antigens, CD / Q000096:biosynthesis* / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics; D007413:Intestinal Mucosa / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D007421:Intestine, Small / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D051917:Leukosialin; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020033:Protein Isoforms / Q000096:biosynthesis / Q000276:immunology; D012795:Sialoglycoproteins / Q000096:biosynthesis* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D017252:CD3 Complex; D016207:Cytokines; D051917:Leukosialin; D020033:Protein Isoforms; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; D016753:Interleukin-10; D007371:Interferon-gamma