title: Immune modulatory effect of thalidomide on T cells.
abstract: BACKGROUND
  Thalidomide was originally used to alleviate morning sickness in pregnant women, but was banned due to severe adverse effects. Since the discovery of its anticancer and anti-inflammatory properties, it has regained research interest. However, its mechanism of action is still unknown. Therefore, we examined the effects of thalidomide on effector T (Teff) and regulatory T (Treg) cells in splenocytes of mice.
  
  
  METHODS
  Splenic CD4(+), CD44(low), and CD62L(high) T lymphocytes (Tnaives) isolated from C57BL/6 mice were cultured for T-cell proliferation and Treg conversion. For T-cell proliferation, naive T cells (Tnaives) were cultured for 72 hours with anti-CD3 and anti-CD28 antibodies, and carboxyfluorescein succinimidyl ester (CFSE) labeling method was used. For Treg conversion, Tnaives were cultured for 72 hours with transforming growth factor-β1 (TGF-β1) and interleukin-2 (IL-2). Naïve T cells were plated at 1.5 × 10(5) cells on 96-well plates with 0, 1, 10, 50, or 100 μmol/L thalidomide. All samples were analyzed by flow cytometry after staining with CFSE, APC-conjugated anti-mouse CD4, and FITC-conjugated anti-mouse FoxP3.
  
  
  RESULTS
  Thalidomide significantly decreased the proliferation of CD4(+) Teffs in a dose-dependent manner (P < .01). In contrast, conversion to CD4(+)FoxP3(+) Tregs tended to increase by thalidomide treatment, although the increase was not statistically significant.
  
  
  CONCLUSIONS
  These findings suggest that thalidomide may have an immune modulatory effect by selectively suppressing CD4(+) Teff proliferation. Further studies will be needed to elucidate the underlying signaling pathway.
authors.affiliation: The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Internal Medicine Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea.
authors.forename: B S
authors.initials: BS
authors.lastname: Kim
authors.affiliation: The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: J Y
authors.initials: JY
authors.lastname: Kim
authors.affiliation: The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea.
authors.forename: J G
authors.initials: JG
authors.lastname: Lee
authors.affiliation: The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Y
authors.initials: Y
authors.lastname: Cho
authors.affiliation: The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea.
authors.forename: K H
authors.initials: KH
authors.lastname: Huh
authors.affiliation: The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea.
authors.forename: M S
authors.initials: MS
authors.lastname: Kim
authors.affiliation: The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Transplantation Surgery, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea. Electronic address: yukim@yuhs.ac.
authors.forename: Y S
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects*; D005434:Flow Cytometry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D013792:Thalidomide / Q000494:pharmacology*
chemical_list: D007166:Immunosuppressive Agents; D013792:Thalidomide