Human and murine lymphocyte neurotrophin expression is confined to B cells.
Recent reports indicate that autoreactive T cells may produce neurotrophic factors capable of mediating repair and regeneration of damaged neurons. By using semiquantitative RT-PCR, we examined gene expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and the trkB BDNF receptor in autoreactive T cells from SWXJ mice immunized with the p104-117 encephalitogen of myelin proteolipid protein (PLP 104-117). We observed antigen-inducible expression of NGF and BDNF, but not NT-3 and trkB, in lymph node cells activated with PLP 104-117. To determine which leukocyte subpopulation expressed neurotrophins, CD4(+), CD8(+), B220(+), CD11b(+), and NK1.1(+) cells were purified from activated primary cultures, and their mRNAs were analyzed. Neurotrophin expression was also measured in CD3(+) T cells purified from mouse CNS during acute onset of experimental autoimmune encephalomyelitis as well as in resting and activated human T cells and B cells purified from peripheral blood of normal subjects. In all cases, we found that neurotrophin expression was confined exclusively to B cells (B220(+)) in both mouse and human. CD3(+), CD4(+), and CD8(+) T cells as well as NK1.1(+) cells and CD11b(+) monocytes and macrophages did not express any detectable BDNF, NGF, NT-3, or trkB under any conditions. Our data indicate that B cells rather than T cells are the predominant if not the only source of leukocyte-derived neurotrophins and as such may provide "protective autoimmunity" in repair and regeneration of the injured nervous system.
Edling
Andrea E
AE
Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Nanavati
Tania
T
Johnson
Justin M
JM
Tuohy
Vincent K
VK
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D015139:Blotting, Southern / Q000379:methods; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D018991:Myelin Proteolipid Protein / Q000276:immunology; D020932:Nerve Growth Factor / Q000378:metabolism; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D020813:Receptor, trkB / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D017422:Sequence Analysis, DNA / Q000379:methods
D019208:Brain-Derived Neurotrophic Factor; D008562:Membrane Glycoproteins; D018991:Myelin Proteolipid Protein; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D010446:Peptide Fragments; D012333:RNA, Messenger; D020932:Nerve Growth Factor; C064371:Ntrk2 protein, mouse; D011505:Protein-Tyrosine Kinases; D020813:Receptor, trkB