@article{19049,
  keywords = {Animals, Cell Division, Cells, Cultured, Drug Synergism, Humans, Immunity, Cellular, Interleukin-12, Interleukin-2, leprosy, Lymphocyte Activation, Mice, Mycobacterium leprae, Recombinant Proteins, T-Lymphocytes},
  author = {Jong R and Janson A A and Faber W R and Naafs B and Ottenhoff T H},
  title = {IL-2 and IL-12 act in synergy to overcome antigen-specific T cell unresponsiveness in mycobacterial disease.},
  abstract = {<p>IL-12 secretion by APC is critical for the development of protective Th1-type responses in mycobacterial (Mycobacterium avium and Mycobacterium tuberculosis) infections in mice. We have studied the role of IL-12 and IL-2 in the generation of Mycobacterium leprae-specific T cell responses in humans. Leprosy patients were defined as low/nonresponders or high responders based on the level of T cell proliferation in M. leprae-stimulated PBMC. In high responders, M. leprae-induced proliferation was markedly suppressed by neutralizing anti-IL-12 mAb (inhibition 55 +/- 6%). Neutralization of IL-2 activity resulted in an inhibition of 77 +/- 4%. Given the importance of endogenous IL-2 and IL-12 in M. leprae-induced responses, we investigated the ability of rIL-2 and rIL-12 to reverse T cell unresponsiveness in low/nonresponder patients. Interestingly, rIL-12 and rIL-2 strongly synergized in restoring both M. leprae-specific T cell proliferation and IFN-gamma secretion almost completely to the level of responder patients. A similar synergy between rIL-2 and rIL-12 was also observed in high responders when suboptimal M. leprae concentrations were used for T cell stimulation. Our data demonstrate a crucial role for endogenous IL-12 and IL-2 in M. leprae-induced T cell activation. Most importantly, we show that rIL-2 and rIL-12 act in synergy to overcome Ag-specific Th1 cell unresponsiveness. These findings may be applicable to the design of antimicrobial and antitumor vaccines.</p>},
  year = {1997},
  journal = {Journal of immunology (Baltimore, Md. : 1950)},
  volume = {159},
  pages = {786-93},
  month = {1997 Jul 15},
  issn = {0022-1767},
  language = {eng},
}