Response of human intestinal lamina propria T lymphocytes to interleukin 12: additive effects of interleukin 15 and 7.
OBJECTIVE
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 beta1 subunit was detected in freshly isolated and activated T-LPLs whereas the beta2 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.
Monteleone
G
G
Dipartimento di Medicina Sperimentale e Clinica, Università di Catanzaro, Catanzaro, Italy.
Parrello
T
T
Luzza
F
F
Pallone
F
F
D018801:CD2 Antigens / Q000494:pharmacology; D018106:CD28 Antigens / Q000494:pharmacology; D002455:Cell Division; D003092:Colitis / Q000276:immunology; D003110:Colonic Neoplasms / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism*; D018664:Interleukin-12 / Q000502:physiology*; D019409:Interleukin-15 / Q000502:physiology*; D015851:Interleukin-7 / Q000502:physiology*; D007413:Intestinal Mucosa / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D018801:CD2 Antigens; D018106:CD28 Antigens; D019409:Interleukin-15; D015851:Interleukin-7; D012333:RNA, Messenger; D018664:Interleukin-12; D007371:Interferon-gamma