@article{1769,
  keywords = {Adult, Aged, Bacterial Proteins, CD56 Antigen, Cells, Cultured, Chaperonin 60, Chaperonins, Cytotoxicity, Immunologic, Down-Regulation, Drug Synergism, Female, Humans, Immune Sera, Interferon-gamma, Interleukin-10, Interleukin-12, Interleukin-4, Interphase, leprosy, Leukocytes, Mononuclear, Lymphocyte Activation, Major Histocompatibility Complex, Male, Middle Aged, Mycobacterium leprae, Protein Binding, T-Lymphocytes, Cytotoxic, Tumor Necrosis Factor-alpha},
  author = {Aleman M and De La Barrera S and Fink S and Finiasz M and Farina M H and Pizzariello G and Sasiain M D},
  title = {Interleukin-12 amplifies the M. leprae hsp65-cytotoxic response in the presence of tumour necrosis factor-alpha and interferon-gamma generating CD56+ effector cells: interleukin-4 downregulates this effect.},
  abstract = {<p>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-alpha and IFN-gamma 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-alpha, IFN-gamma 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-gamma and TNF-alpha 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-gamma and did not modify that of TNF-alpha so the low CTL activity could be as a result of IL-4 by a decrease of the IFN-gamma binding on MB cells. Cells from those MB patients taking thalidomide (MB-T) did neither bind IFN-gamma nor TNF-alpha even when antigen or anti-IL-4 were added, demonstrating that thalidomide inhibits either the in vitro binding or receptor expression of both TNF-alpha and IFN-gamma. Development of CD56 effector cells during the hsp65 stimulation was observed in PB and N by the addition of IL-12 plus TNF-alpha and IFN-gamma, while in MB and MB-T anti IL-4 was also required. So, the inhibitory effect of IL-4 on either production of IFN-gamma, TNF-alpha and/or IL-12 or their receptors could be the mechanism underlying the lack of the hsp65 CTL generation in cells from MB.</p>},
  year = {2000},
  journal = {Scandinavian journal of immunology},
  volume = {51},
  pages = {262-70},
  month = {2000 Mar},
  issn = {0300-9475},
  doi = {10.1046/j.1365-3083.2000.00675.x},
  language = {eng},
}