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GUT 1998;43:620-628 ( November )

Response of human intestinal lamina propria T lymphocytes to interleukin 12: additive effects of interleukin 15 and 7

G Monteleone, T Parrello, F Luzza, F Pallone

Dipartimento di Medicina Sperimentale e Clinica, Università di Catanzaro, Catanzaro, Italy

Correspondence to: Dr F Pallone, Cattedra di Gastroenterologia, Dipartimento di Medicina Sperimentale, Policlinico Universitario, Via T Campanella, 88100 Catanzaro, Italy.

Accepted for publication 13 May 1998

Background/Aim---Interleukin (IL) 12 is involved in the mucosal response during intestinal inflammation but its role is not fully understood. The response of human lamina propria T lymphocytes (T-LPL) to IL-12 in terms of interferon gamma  (IFN-gamma ) release and proliferation was investigated, exploring whether IL-15 and IL-7 cooperate with IL-12. The role of accessory molecules (CD2 and CD28) was also investigated.
Methods---Unstimulated and phytohaemagglutinin preactivated T-LPL cultures were incubated with or without the initial addition of cytokines, anti-CD2 or anti-CD28 antibodies. IFN-gamma mRNA was detected by reverse transcriptase polymerase chain reaction, and protein secretion was measured by enzyme linked immunosorbent assay (ELISA).
Results---IFN-gamma mRNA was induced in T-LPLs by IL-12 and IL-15 but not IL-7, whereas IFN-gamma was measured only in IL-12 stimulated T-LPL cultures. IL-12 induced IFN-gamma release was not abrogated by neutralising anti-IL-2 antibody or by cyclosporin A. IL-12 synergised with either anti-CD2 or anti-CD28 antibodies in inducing IFN-gamma synthesis. In preactivated T-LPLs, IL-7 enhanced IFN-gamma release induced by both IL-12 and anti-CD2, whereas IL-15 potentiated only IL-12 induced IFN-gamma synthesis. IL-12 did not induce proliferation of either unstimulated or preactivated T-LPLs and it did not enhance the CD2/CD28 stimulated T-LPL proliferative response. No transcript for IL-12 receptor beta 1 subunit was detected in freshly isolated and activated T-LPLs whereas the beta 2 subunit mRNA was consistently found in T-LPL samples.
Conclusions---IL-12 induces human T-LPLs to produce and release IFN-gamma , and IL-15 and IL-7 cooperate with IL-12 in expanding the IFN-gamma mucosal response.
(GUT 1998;43:620-628)

Keywords: interleukin 12;  interleukin 7;  interleukin 15;  interferon gamma ;  intestinal inflammation


© 1998 by Gut



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