B S Kim1, J Y Kim2, J G Lee3, Y Cho2, K H Huh3, M S Kim3, Y S Kim4. 1. 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. 2. The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea. 3. 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. 4. 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.
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. CONCLUSION: 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.
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-mouseCD4, and FITC-conjugated anti-mouseFoxP3. 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. CONCLUSION: 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: Soo Jin Kim; Joon Ye Kim; Eun Jee Kim; Hyojung Lee; Yuri Cho; Myoung Soo Kim; Yu Seun Kim; Beom Seok Kim; Kyu Ha Huh Journal: Yonsei Med J Date: 2022-02 Impact factor: 2.759