Suppression of T-cell activation in vitro and in vivo by cordycepin from Cordyceps militaris.
BACKGROUND
In addition to achieving a balance between the positive (controlling rejection) and the negative (infection and malignancy) aspects of drug-induced immunodeficiency, new immunosuppressive combinations must address the issue of nonimmune drug toxicity that may be dose limiting. Cordycepin is a type of adenosine analog extracted from Cordyceps militaris. In the present study, we investigated its immunosuppressive effect on T cell both in vitro and in vivo.


METHODS
We evaluated the effects of cordycepin on concanavalin A-induced production of immune mediators in mouse splenocyte by enzyme-linked immunosorbent assay and flow cytometry. Furthermore, using Western blotting, we studied signal transduction mechanisms to determine how cordycepin inhibited T-cell activation in purified mouse T lymphocytes. To confirm the immunosuppressive activity of cordycepin in vivo, we induced the T cell-mediated delayed-type hypersensitivity reaction in a 2,4-dinitro-1-fluorobenzene-induced mouse model.


RESULTS
The in vitro results showed that cordycepin markedly suppressed concanavalin A-induced splenocyte proliferation, Th1 and Th2 cytokine production, and the ratio of CD4(+)-to-CD8(+) T cells. The administration of cordycepin in vivo markedly suppressed the T cell-mediated delayed-type hypersensitivity reaction. The data revealed that cordycepin effectively shocked the nuclear factor kappa B and nuclear factor of activated T cells 2 signal transduction pathways but had no effect on the mitogen activated protein kinase signal transduction pathway.


CONCLUSIONS
These observations indicated that cordycepin has a potential role in downregulating the immune system and could be developed as a useful immunosuppressive agent for treating undesired immune responses.
Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, Jilin, People's Republic of China.
Ying
Y
Xiong
Shuang
S
Zhang
Linli
L
Xu
Bocui
B
Song
Guoren
G
Huang
Jing
J
Lu
Shuang
S
Guan
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D003208:Concanavalin A / Q000494:pharmacology; D032661:Cordyceps / Q000737:chemistry*; D003839:Deoxyadenosines / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005434:Flow Cytometry; D006968:Hypersensitivity, Delayed / Q000188:drug therapy / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000494:pharmacology; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000166:cytology
D000970:Antineoplastic Agents; D003839:Deoxyadenosines; D004365:Drugs, Chinese Herbal; D007166:Immunosuppressive Agents; D008934:Mitogens; D016328:NF-kappa B; D003208:Concanavalin A; C058120:cordycepin
CD4(+)/CD8(+); Cordycepin; Cytokines; DTH; NF-қB; NFAT2