Absence of preproenkephalin increases the threshold for T cell activation.
Certain forms of the neuroendocrine hormone preproenkephalin (PPNK) are produced by T cells, B cells and macrophages. This hormone has been shown to be important in regulating a variety of immune responses; however, the basic mechanisms of this regulation are unknown. Here we examine the ability of CD8 and CD4 PPNK-deficient T lymphocytes to proliferate to antigenic and mitogenic stimuli. We found that lymphocyte activation and proliferation to suboptimal concentrations of both anti-CD3 and antigen was reduced in the absence of PPNK. Proliferation could be rescued by increasing antigen or by co-incubation of PPNK-deficient cells with wild-type cells. These data confirm the importance of neuroendocrine hormones such as PPNK in T cell activation and proliferation and provides a potential mechanism for the regulation of T cell responses by PPNK or its peptide derivatives.
Hook
Sarah
S
School of Pharmacy, University of Otago, P.O. Box 913, Dunedin, New Zealand. sarah.hook@stonebow.otago.ac.nz
Camberis
Mali
M
Prout
Melanie
M
Le Gros
Graham
G
D000818:Animals; D000941:Antigens / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D000956:Antigens, Viral / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D004745:Enkephalins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D008213:Lymphocyte Activation / Q000235:genetics*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016853:Muromonab-CD3 / Q000502:physiology; D011498:Protein Precursors / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
D000941:Antigens; D000945:Antigens, Differentiation, T-Lymphocyte; D000956:Antigens, Viral; D016207:Cytokines; D004745:Enkephalins; D016853:Muromonab-CD3; D011498:Protein Precursors; D015375:Receptors, Interleukin-2; C033660:preproenkephalin