The modulation of thymosin alpha 1 in the maturation, differentiation and function of murine bone marrow-derived dendritic cells in the absence or presence of tumor necrosis factor-alpha.
Thymosin alpha 1 (Talpha1) has immunomodulatory effects on T-cells, NK-cells and macrophages, but its action on dendritic cells (DCs), which are recognized as the sole professional antigen presenting cells (APCs) capable of priming naïve T-cells, is poorly understood. In this study, the effect of Talpha1 in vitro on murine bone marrow-derived DCs (BMDCs) maturation, differentiation, and function with or without tumor necrosis factor-alpha (TNF-alpha), which is one of the important inflammatory parameters, has been investigated. We have shown, through flow cytometry, ELISA and mixed leukocyte reaction (MLR), that Talpha1 promoted CD4-expressed DC differentiation and the expression of activation markers, but did not influence IL-12 production and T cell-stimulatory capacity of DCs in the absence of TNFalpha during BMDCs maturation. Furthermore, in the presence of TNF-alpha, Talpha1 has been shown not only to promote the expression of CD4 on MHC class II+ DCs and enhance the up-regulated levels of mature markers induced by TNF-alpha, but also to suppress the up-regulated IL-12 production. Particularly, thus effects seen were obvious at pharmacological Talpha1 concentrations. However, Talpha1 did not inhibit TNF-alpha-induced T-cell stimulating function of DCs. This is the first reported example of a direct Talpha1-DC interaction and suggests a mechanism by which Talpha1 may in part affect T-cell responses by acting at the DC level and it may play an important role in the modulation of the local inflammatory responses in vivo.
Huang
Yin
Y
Institute of Infectious Diseases, First Affiliated Hospital, Medical College, Zhejiang University, Qingchun Road 79 Hangzhou 310003, People's Republic of China.
Chen
Zhi
Z
Zhou
Cheng
C
Yao
Hangping
H
Li
Minwei
M
Xu
Chenghuai
C
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*
D000276:Adjuvants, Immunologic; D015704:CD4 Antigens; D016827:CD8 Antigens; D000949:Histocompatibility Antigens Class II; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D013947:Thymosin; D000077596:Thymalfasin