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- Title
Interleukin-12 Amplifies the M. leprae hsp65-Cytotoxic Response in the Presence of Tumour Necrosis Factor-α and Interferon-γ Generating CD56[sup +] Effector Cells: Interleukin-4 Downregulates This Effect.
- Authors
Aleman; De La Barrera; Fink; Finiasz; Farina; Pizzariello; Sasiain
- Abstract
Interleukin-12 (IL-12) is a major immunomodulatory cytokine that represents a functional bridge between the early resistance and the subsequent antigen specific adaptive immunity. TNF-α and IFN-γ have an important role in the generation of hsp65 specific cytotoxic T lymphocytes (CTL) that lyse hsp65-pulsed autologous macrophages (hsp65 CTL). Since a positive feedback mechanism between TNF-α, IFN-γ and IL-12 has been described, we undertook to evaluate the role of IL-12 on the hsp65 CTL generation in leprosy patients. Our results show that the presence of IL-12 during the first 24 h of the in vitro antigen stimulation amplifies the hsp65 cytotoxic response whenever both IFN-γ and TNF-α are present. The addition of these three cytokines (CKs) was able to abrogate the inhibitory effect of IL-10 on hsp65 CTL in cells from paucibacillary patients (PB) but not that of IL-4 in PB and normal controls (N). Both IL-12 or anti IL-4 enhanced the cytotoxic activity in cells from multibacillary patients (MB). Anti IL-4 upregulated the binding of IFN-γ and did not modify that of TNF-α so the low CTL activity could be as a result of IL-4 by a decrease of the IFN-γ binding on MB cells. Cells from those MB patients taking thalidomide (MB-T) did neither bind IFN-γ nor TNF-α even when antigen or anti-IL-4 were added, demonstrating that thalidomide inhibits either the in vitro binding or receptor expression of both TNF-α and IFN-γ. Development of CD56 effector cells during the hsp65 stimulation was observed in PB and N by the addition of IL-12 plus TNF-α and IFN-γ, while in MB and MB-T anti IL-4 was also required. So, the inhibitory effect of IL-4 on either production of IFN-γ, TNF-α and/or IL-12 or their receptors could be the mechanism underlying the lack of the hsp65 CTL generation in cells from MB.
- Subjects
INTERLEUKIN-12; HANSEN'S disease; CYTOKINES
- Publication
Scandinavian Journal of Immunology, 2000, Vol 51, Issue 3
- ISSN
0300-9475
- Publication type
Article