Influence of a DLE-extracted lymphocytic suppressor factor on CsA-induced immunosuppression

Area of Science:

• Immunology
• Molecular Biology

Background:

• Dialyzable leukocyte extracts (DLE) contain bioactive factors.
• Lymphocyte transformation and allograft survival are key immune responses.

Purpose of the Study:

• To purify and characterize a novel immunosuppressive factor from DLE.
• To investigate the molecular mechanisms and in vivo effects of this factor.

Main Methods:

• Purification of a low-molecular-weight factor from DLE.
• Assays for lymphocyte transformation and allograft survival in mice.
• In vitro studies on DNA replication and transcription inhibition.
• Amino acid analysis of the purified factor.
• In vivo studies combining the factor with cyclosporine A.

Main Results:

• A hydrophilic, low-mol. wt. (approx. 1 kDa) peptide, termed lymphocytic suppressor factor (LSF), was isolated.
• LSF suppresses antigen- and mitogen-induced lymphocyte transformation and prolongs skin allograft survival in mice.
• LSF inhibits DNA replication and transcription in activated lymphocytes and cell-free systems.
• LSF potentiates the immunosuppressive effects of cyclosporine A in vitro and in vivo.
• LSF levels correlate with cyclosporine A-induced immunosuppression in mice.

Conclusions:

• LSF is a peptide factor that inhibits lymphocyte proliferation and DNA processes.
• LSF plays a significant role in cyclosporine A-mediated immunosuppression.
• LSF may be involved in the pathogenesis of AIDS by affecting lymphocyte DNA processes.