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Updated: Aug 9, 2026
In Vitro and In Vivo Assessment of T, B and Myeloid Cells Suppressive Activity and Humoral Responses from Transplant Recipients
Published on: August 12, 2017
Influence of a DLE-extracted lymphocytic suppressor factor on CsA-induced immunosuppression
V E Rosso di San Secondo1, A Aniasi, G Piccolo
1Transplantation Immunology and Blood Transfusion Center, University-Hospital Policlinico, Milano, Italy.
Insights
A novel lymphocytic suppressor factor (LSF) inhibits lymphocyte proliferation and prolongs allograft survival. LSF enhances cyclosporine A
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.
Abstract:
From dialyzable leucocyte extracts (DLE) we have purified a hydrophilic low-mol. wt. factor (about 1 kDa) which we have named lymphocytic suppressor factor (LSF) as it is able to suppress antigen- and mitogen-induced lymphocyte transformation and to prolong allograft survival in C57b/6N mice (H-2b) transplanted with fully mismatched skin from C3H/HeN mice (H-2k). At the molecular level LSF acts by inhibiting DNA replicational and transcriptional processes in activated lymphocytes, isolated rat hepatocyte nuclei, and cell-free systems. Amino acid analysis indicates that LSF is a peptide composed of Asp, Glu, Ser, Thr, Ala, Gly, Arg and probably Met, with the N-terminus blocked, possibly by pyroglutamic acid. When combined "in vitro" with cyclosporine A (CsA), LSF increased about 20 times the potency of CsA in inducing suppression of mitogen-stimulated lymphocytes. In C57b/6N mice with skin graft from C3H/HeN mice and undergoing immunosuppression with CsA (50 mg/kg/day), the splenocyte LSF content increased about 5 times. However, LSF values returned to normal in mice recovering normal responsiveness due to progressive withdrawal of CsA. These data show that LSF has an important role in the development and maintenance of CsA-induced immunosuppression. We suggest that, by influencing DNA replicational and transcriptional processes of lymphocytes, LSF may play a role also in the onset and progression of AIDS induced by retroviruses.
