Abstract
Intestinal T-cell lines were generated from lamina propria mononuclear cells isolated from colonoscopic biopsies in ulcerative colitis patients and controls. In both ulcerative colitis and controls, expanded cells were constituted largely by T-cell receptor αβ+, CD4+, CD45RA− (helper), and CD8+, CD11b− (cytotoxic) phenotypes. T-cell receptor Vβ gene usage was not significantly changed after cell expansion and no difference was observed between ulcerative colitis and controls. Ulcerative colitis cells, especially those derived from the patients with long-standing disease, showed significantly higher levels of cytotoxicity against the target cells, including those of colonic epithelial origin, and enhanced production of tumor necrosis factor-α and interferon-γ after short incubation with anti-CD3 antibody. Generation of T-cell lines from colonoscopic biopsy specimens may be useful for detailed functional characterization of locally infiltrating T cells in ulcerative colitis patients.
Similar content being viewed by others
References
Fiocchi C: Immunology of inflammatory bowel disease. Curr Opinion Gastroenterol 7:654–661, 1991
Podolsky DK: Inflammatory bowel disease. First of two parts. N Engl J of Med 325:928–937, 1991
Ferguson A, Jarrett EEE: Hypersensitivity reactions in the small intestine. I. Thymus dependence of experimental “partial villous atrophy.” Gut 16:114–117, 1975
D'Inca R, Ernst P, Hunt RH, Perdue MH: Role of T lymphocytes in intestinal mucosal injury. Inflammatory changes in athymic nude rats. Dig Dis Sci 37:33–39, 1992
Guy-Grand D, Vassalli P: Gut injury in mouse graft-versus-host reaction. Study of its occurrence and mechanisms. J Clin Invest 77:1584–1595, 1986
MacDonald TT, Spencer J: Evidence that activated mucosal T cells play a role in the pathogenesis of enteropathy in human small intestine. J Exp Med 167:1341–1349, 1988
Deem RL, Shanahan F, Targan SR: Triggered human mucosal T cells release tumour necrosis factor-alpha and interferon-gamma which kill human colonic epithelial cells. Clin Exp Immunol 83:79–84, 1991
Kvale D, Brandtzaeg P, Løvhaug D: Up-regulation of the expression of secretory component and HLA molecules in a human colonic cell line by tumour necrosis factor-α and gamma interferon. Scand J Immunol 28:351–357, 1988
Crotty B, Hoang P, Dalton HR, Jewell DP: Salicylates used in inflammatory bowel disease and colchicine impair interferon-γ induced HLA-DR expression. Gut 33:59–64, 1992
Olson AD, Ayass M, Chensue S: Tumor necrosis factor and IL-1β expression in pediatric patients with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 16:241–246, 1993
Breese E, Braegger CP, Corrigan CJ, Walker-Smith JA, MacDonald TT: Interleukin-2- and interferon-γ-secreting T cells in normal and diseased human intestinal mucosa. Immunology 78:127–131, 1993
Pallone F, Fais S, Squarcia O, Biancone L, Pozzilli P, Boirivant M: Activation of peripheral blood and intestinal lamina propria lymphocytes in Crohn's disease.In vivo state of activation andin vitro response to stimulation as defined by the expression of early activation antigens. Gut 28:745–753, 1987
Choy MY, Walker-Smith JA, Williams CB, MacDonald TT: Differential expression of CD25 (interleukin-2 receptor) on lamina propria T cells and macrophages in the intestinal lesions in Crohn's disease and ulcerative colitis. Gut 31:1365–1370, 1990
Schreiber S, MacDermott RP, Raedler A, Pinnau R, Bertovich MJ, Nash GS: Increased activation of isolated intestinal lamina propria mononuclear cells in inflammatory bowel disease. Gastroenterology 101:1020–1030, 1991
Haruta J, Kusugami K, Kuroiwa A, Ina K, Shinoda M, Morise K, Iokawa H, Morita M, Ishihara A, Sarai S: Phenotypic and functional analysis of lamina propria mononuclear cells from colonoscopic biopsy specimens in patients with ulcerative colitis. Am J Gastroenterol 87:448–454, 1992
Roche JK, Fiocchi C, Youngman K: Sensitization to epithelial antigens in chronic mucosal inflammatory disease. Characterization of human intestinal mucosa-derived mononuclear cells reactive with purified epithelial cell-associated componentsin vitro. J Clin Invest 75:522–530, 1985
Shanahan F, Deem R, Nayersina R, Leman B, Targan S: Human mucosal T-cell cytotoxicity. Gastroenterology 94:960–967, 1988
Fiocchi C, Tubbs RR, Youngman KR: Human intestinal mucosal mononuclear cells exhibit lymphokine-activated killer cell activity. Gastroenterology 88:625–637, 1985
MacDermott RP, Bragdon MJ, Kodner IJ, Bertovich MJ: Deficient cell-mediated cytotoxicity and hyporesponsiveness to interferon and mitogenic lectin activation by inflammatory bowel disease peripheral blood and intestinal mononuclear cells. Gastroenterology 90:6–11, 1986
Gibson PR, Van de Pol E, Pullman W, Doe WF: Lysis of colonic epithelial cells by allogeneic mononuclear and lymphokine activated killer cells derived from peripheral blood and intestinal mucosa: Evidence against a pathogenic role in inflammatory bowel disease. Gut 29:1076–1084, 1988
Kusugami K, Youngman KR, West GA, Fiocchi C: Intestinal immune reactivity to interleukin 2 differs among Crohn's disease, ulcerative colitis, and controls. Gastroenterology 97:1–9, 1989
Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159, 1987
Sottini A, Imberti L, Gorla R, Cattaneo R, Primi D: Restricted expression of T cell receptor Vβ but not Vα genes in rheumatoid arthritis. Eur J Immunol 21:461–466, 1991
Kaulfersch W, Fiocchi C, Waldmann TA: Polyclonal nature of the intestinal mucosal lymphocyte populations in inflammatory bowel disease. A molecular genetic evaluation of the immunoglobulin and T-cell antigen receptors. Gastroenterology 95:364–370, 1988
Pross HF, Baines MG, Rubin P, Shragge P, Patterson MS: Spontaneous human lymphocyte-mediated cytotoxicity against tumor target cells. IX. The quantitation of natural killer cell activity. J Clin Immunol 1:51–63, 1981
Kusugami K, Matsuura T, West GA, Youngman KR, Rachmilewitz D, Fiocchi C: Loss of interleukin-2-producing intestinal CD4+ cells in inflammatory bowel disease. Gastroenterology 101:1594–1605, 1991
Miyazaki H, Kawasaki H, Hirayama C: Studies on lymphocyte subpopulations in human colonic biopsy specimens by colonoscopy. Dig Dis Sci 30:143–148, 1985
Comer GM, Ramey WG, Kotler DP, Holt PR: Isolation of intestinal mononuclear cells from colonoscopic biopsies for immunofluorescence analysis by flow cytometry. Dig Dis Sci 31:151–156, 1986
Kappler J, Kotzin B, Herron L, Gelfand EW, Bigler RD, Boylston A, Carrel S, Posnett DN, Choi Y, Marrack P: Vβ-specific stimulation of human T cells by Staphylococcal toxins. Science 244:811–813, 1989
Fukushima K, Masuda T, Ohtani H, Sasaki I, Funayama Y, Matsuno S, Nagura H: Immunohistochemical characterization, distribution, and ultrastructure of lymphocytes bearing T-cell receptor γ/δ in inflammatory bowel disease. Gastroenterology 101:670–678, 1991
Buckle AM, Hogg N: Human memory T cells express intercellular adhesion molecule-1 which can be increased by interleukin 2 and interferon-γ. Eur J Immunol 20:337–341, 1990
Kelleher D, Kagnoff MF: Development and characterisation of T lymphocyte lines from human small intestinal biopsies. Gut 30:460–467, 1989
Ito M, Ajitsu S, Fuyama S, Takahashi T, Ishikawa M, Arai S: Production of TNF-α, GM-CSF, IFNγ by human gut mucosal T cell lines in response to CD3 cross-linking and IL-2.In Frontiers of Mucosal Immunology, Vol. 1. M Tsuchiya, H Nagura, T Hibi, I Moro (eds). Amsterdam, Elsevier Science Publishers, 1991, pp 83–84
Quiding M, Nordström I, Larsson L, Andersson G, Russel MW, Jonsson R, Svennerholm AM, Hansson LA, Kilander A, Granström G, Friman W, Holmgren J, Czerkinsky C: The cellular basis of intestinal immunity in humans.In Frontiers of Mucosal Immunology, Vol 1. M Tsuchiya, H Nagura, T Hibi, I Moro (eds). Amsterdam, Elsevier Science Publishers, 1991, pp 255–259
Volk BA, Niessner M, Fauser AA, Kanz L, Wolff-Vorbeck G, Gerok W: Functional and phenotypic characterization of intestinal T cell subpopulations derived from human gut biopsies in patients with inflammatory bowel disease.In Frontiers of Mucosal Immunology, Vol 1. M Tsuchiya, H Nagura, T Hibi, I Moro (eds). Amsterdam, Elsevier Science Publishers, 1991, pp 767–769
James SP, Fiocchi C, Graeff AS, Strober W: Phenotypic analysis of lamina propria lymphocytes. Predominance of helper-inducer and cytolytic T-cell phenotypes and deficiency of suppressor-inducer phenotypes in Crohn's disease and control patients. Gastroenterology 91:1483–1489, 1986
Shanahan F, Brogan M, Targan S: Human mucosal cytotoxic effector cells. Gastroenterology 92:1951–1957, 1987
Fiocchi C, Youngman KR, Yen-Lieberman B, Tubbs RR: Modulation of intestinal immune reactivity by interleukin 2. Phenotypic and functional analysis of lymphokine-activated killer cells from human intestinal mucosa. Dig Dis Sci 33:1305–1315, 1988
Yagita H, Nakata M, Azuma A, Nitta T, Takeshita T, Sugamura K, Okumura K: Activation of peripheral blood T cells via the p75 interleukin 2 receptor. J Exp Med 170:1445–1450, 1989
Phillips JH, Lanier LL: Lectin-dependent and anti-CD3 induced cytotoxicity are preferentially mediated by peripheral blood cytotoxic T lymphocytes expressing Leu-7 antigen. J Immunol 136:1579–1585, 1986
Mayer L, Eisenhardt D: Lack of induction of suppressor T cells by intestinal epithelial cells from patients with inflammatory bowel disease. J Clin Invest 86:1255–1260, 1990
Shanahan F, Leman B, Deem R, Niederlehner A, Brogan M, Targan S: Enhanced peripheral blood T-cell cytotoxicity in inflammatory bowel disease. J Clin Immunol 9:55–64, 1989
Choi Y, Kotzin B, Herron L, Callahan J, Marrack P, Kappler J: Interaction of Staphylococcus aureus toxin “super-antigens” with human T cells. Proc Natl Acad Sci USA 86:8941–8945, 1989
Spencer J, Choy MY, MacDonald TT: T cell receptor Vβ expression by mucosal T cells. J Clin Pathol 44:915–918, 1991
Lehmann PV, Forsthuber T, Miller A, Sercarz EE: Spreading of T-cell autoimmunity to cryptic determinants of an autoantigen. Nature 358:155–157, 1992
Turner M, Londei M, Feldmann M: Human T cells from autoimmune and normal individuals can produce tumor necrosis factor. Eur J Immunol 17:1807–1814, 1987
Leeuwenberg JFM, Damme JV, Meager T, Jeunhomme TMAA, Buurman WA: Effects of tumor necrosis factor on the interferon-γ-induced major histocompatibility complex class II antigen expression by human endothelial cells. Eur J Immunol 18:1469–1472, 1988
Campbell IL, Iscaro A, Harrison LC: IFN-γ and tumor necrosis factor-α. Cytotoxicity to murine islets of Langerhans. J Immunol 141:2325–2329, 1988
James SP, Kwan WC, Sneller MC: T cells in inductive and effector compartments of the intestinal mucosal immune system of nonhuman primates differ in lymphokine mRNA expression, lymphokine utilization, and regulatory function. J Immunol 144:1251–1256, 1990
Kooten CV, Rensink I, Pascual-Salcedo D, Oers RV, Aarden L: Monokine production by human T cells; IL-1α production restricted to memory T cells. J Immunol 146:2654–2658, 1991
Evans CM, Phillips AD, Walker-Smith JA, MacDonald TT: Activation of lamina propria T cells induces crypt epithelial proliferation and goblet cell depletion in cultured human fetal colon. Gut 33:230–235, 1992
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kusugami, K., Haruta, JI., Ieda, M. et al. Phenotypic and functional characterization of T-cell lines generated from colonoscopic biopsy specimens in patients with ulcerative colitis. Digest Dis Sci 40, 198–210 (1995). https://doi.org/10.1007/BF02063967
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02063967