Abstract
Human intestinal lymphocytes, particularly intraepithelial lymphocytes, proliferate minimally to some agents, like mitogens and stimuli of the CD3 pathway. Thisin vitro finding may be due, in part, to a loss of factors foundin vivo. Three T-cell growth factors, IL-7, IL-9, and IL-12, were tested for their ability to stimulate the proliferation of intestinal lymphocytes. Both intraepithelial lymphocytes and lamina propria lymphocytes proliferated more vigorously to IL-7 than to IL-9 or IL-12, and only IL-7 increased stimulation through the CD3 pathway. The IL-7-induced response was IL-2-dependent: IL-2 receptors appeared on both intestinal lymphocyte types, and antibody to the IL-2 receptor blocked IL-7-induced proliferation. Both CD4+ and CD8+ T-cell subsets responded to this cytokine as shown by phenotype-depletion experiments and constancy in the CD4/CD8 ratios after culture with IL-7. In addition, the T-cell receptor αβ and γδ subsets responded equally well to IL-7. This newly described selective proliferative response of intestinal lymphocytes to IL-7, but not to IL-9 or IL-12, requires no preactivation and may enhance, growthin vivo.
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Ebert EC: Proliferative responses of human intraepithelial lymphocytes to various T-cell stimuli. Gastroenterology 97:1372–1381, 1989
Qiao L, Schurmann G, Betzler M, Meuer SC: Activation and signaling status of human lamina propria T lymphocytes. Gastroenterology 101:1529–1536, 1991
Nadler SC, Roberts AI, Ebert EC: Mesenchymal cells are potent accessory cells for human intraepithelial lymphocytes. Gastroenterology 104:A752, 1992
Roberts AI, O'Connell SM, Ebert EC: Intestinal intraepithelial lymphocytes bind to colon cancer cells by HML-1 and CD11a. Cancer Res 53:1608–1611, 1993
Marks PW, Maxfield FR: Transient increases in cytosolic free calcium appear to be required for the migration of adherent human neutrophils. J Cell Biol 110:43–52, 1990
Grabstein KH, Namen AE, Shanebeck K, Voice RF, Reed SG, Widmer MB: Regulation of T cell proliferation by IL-7. J Immunol 144:3015–3020, 1990
Morrissey PJ, Goodwin RG, Nordan RP, Anderson D, Grabstein KH, Cosman D, Sims J, Lupton S, Acres B, Reed SG, Mochizuki D, Eisenman J, Conlon PJ, Namen AE: Recombinant interleukin 7, pre-B cell growth factor, has costimulatory activity on purified mature T cells. J Exp Med 169:707–716, 1989
Houssiau FA, Rensuld J-C, Stevens M, Lehmann F, Lethe B, Coulie PG, Van Snick J: Human T cell lines and clones respond to IL-9. J Immunol 150:2634–2640, 1993
Gately MK, Desai BB, Wolitzky AG, Quinn PM, Dwyer CM, Podlaski FJ, Familletti PC, Sinigaglia F, Chizonnite R, Gubler U, Stern AS: Regulation of human lymphocyte proliferation by a heterodimeric cytokine, IL-12 (cytotoxic lymphocyte maturation factor). J Immunol 147:874–882, 1991
Matsue H, Bergstresser PR, Takashima A: Keratinocytederived IL-7 serves as a growth factor for dendritic epidermal T cells in mice. J Immunol 151:6012–6019, 1993
Plum J, De Smedt M, Leclercq G Exogenous IL-7 promotes the growth of CD3−CD4−CD8− CD44+CD25± precursor cells and blocks the differentiation pathway of TCR-αβ cells in fetal thymus organ culture. J Immunol 150:2706–2716, 1993
Watanabe Y, Sudo T, Minato N, Ohnishi A, Katsura Y: Interleukin 7 preferentially supports the growth of gamma delta T-cells from fetal thymocytes in vitro. Int Immunol 3:1067–1075, 1991
Namen AE, Lupton S, Hjerrild K, Wignall J, Mochizuki DY, Schmierer B, Mosley B, March CJ, Urdal D, Gillis S, Cosman D, Goodwin RG: Stimulation of B cell progenitors by cloned murine IL-7. Nature 333:571–573, 1988
Ueno Y, Watanabe M, Yajima T, Ezaki S, Takaishi H, Inoue N, Iwoa Y, Tsuchiya M, Ishikawa H, Aiso S, Hibi T: IL-7 is produced by human intestinal epithelial globlet cells. Gastroenterology 106:A787, 1994 (abstract)
Conlon PJ, Morrissey PJ, Nordan RP, Grabstein KH, Prickett KS, Reed SG, Goodwin R, Cosman D, Namen AE: Murine thymocytes proliferate in direct response to interleukin-7. Blood 74:1368–1373, 1989
Schmitt E, Beuscher HU, Huels C, Monteyne P, van Brandwijk R, van Snick J, Ruede E: IL-1 serves as a secondary signal for IL-9 expression. J Immunol 147:3848–3854, 1991
D'Andrea A, Rengaraju M, Valiante NM, Chehimi J, Kubin M, Aste M, Chan SH, Kobayashi M, Young D, Nickbarg E, Chizzonite R, Wolf SF, Trinchieri G: Production of natural killer cell stimulatory factor (interleukin-12) by peripheral blood mononuclear cells. J Exp Med 176:1387, 1992
Quill H, Bhandoola A, Trinchieri G, Haluskey J, Peritt, D: Induction of interleukin 12 responsiveness is impaired in anergic T lymphocytes. J Exp Med 179:1065–1070, 1994
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This work was supported by grants from the Crohn's & Colitis Foundation of America and the National Institutes of Health (DK42166).
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Bilenker, M., Roberts, A.I., Brolin, R.E. et al. Interleukin-7 activates intestinal lymphocytes. Digest Dis Sci 40, 1744–1749 (1995). https://doi.org/10.1007/BF02212696
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DOI: https://doi.org/10.1007/BF02212696