Role of Thalidomide on the Expression of OX40, 4-1BB, and GITR in T Cell Subsets.
BACKGROUND
Thalidomide (TM) is known to have anti-cancer and anti-inflammatory properties; however, its mechanism on T cells is still unclear. We previously showed the immune modulatory effect of TM on T cells and its therapeutic effect on lupus nephritis models. Here we examined the changes in the expression of tumor necrosis factor receptor superfamilies (TNFRSFs), including OX40, 4-1BB, and glucocorticoid-induced TNFR-related protein (GITR) in T cell subsets by TM treatments.


METHODS
Splenic naïve T cells (Tnaives) from C57BL/6 mice were sort-purified and cultured for CD4(+) T cell proliferation and regulatory T cells (Tregs) conversion with TM treatments. All samples were analyzed by flow cytometry after stained with anti-mouse CD4, Foxp3, OX40, 4-1BB, or GITR antibodies.


RESULTS
Expressions of OX40, 4-1BB, and GITR on CD4(+) T cells showed a decreasing tendency by TM treatments. Especially, downregulation of these molecules on CD4(+)CFSE(low) T cells was significant in TM treatment groups. On the condition of Treg conversion, OX40 was downregulated significantly. In contrast, the expression of GITR was increased, and that of 4-1BB had shown no particular change under the condition of Treg.


CONCLUSIONS
Considering these results, TM may have an immune modulatory role through the T cell subset-specific change of OX40, 4-1BB, and GITR expression. Further study is required to elucidate the effect of thalidomide on T cells.
The Research Institute for Transplantation, Yonsei University College of Medicine Seoul, Republic of Korea; Division of Nephrology, Department of Internal Medicine Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea.
B S
BS
Kim
The Research Institute for Transplantation, Yonsei University College of Medicine Seoul, Republic of Korea.
J Y
JY
Kim
The Research Institute for Transplantation, Yonsei University College of Medicine Seoul, Republic of Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Republic of Korea.
E J
EJ
Kim
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.
J G
JG
Lee
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.
D J
DJ
Joo
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.
K H
KH
Huh
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.
M S
MS
Kim
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.
Y S
YS
Kim
D053330:4-1BB Ligand / Q000378:metabolism*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D053450:Glucocorticoid-Induced TNFR-Related Protein / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D053262:Receptors, OX40 / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D013792:Thalidomide / Q000494:pharmacology*
D053330:4-1BB Ligand; D053450:Glucocorticoid-Induced TNFR-Related Protein; D007166:Immunosuppressive Agents; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505717:Tnfrsf4 protein, mouse; D013792:Thalidomide