Human and murine lymphocyte neurotrophin expression is confined to B cells

Abstract

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.

Loss of islet sympathetic nerves and impairment of glucagon secretion in the NOD mouse: relationship to invasive insulitis

“…Because blocking the invasive insulitis by CFA treatment prevented the loss of islet sympathetic nerves, we conclude that the invading lymphocytes are required for this nerve loss. Further studies are needed to determine whether this lymphocyte-mediated nerve loss is due to cytotoxic Tlymphocytes targeting an autoantigen on sympathetic nerve terminals, to the release of neurotoxic cytokines from invading lymphocytes [41] or to the release of anti-sympathetic neurotropins [42] from invading B-lymphocytes [43].…”

HBZ Stimulates Brain-Derived Neurotrophic Factor/TrkB Autocrine/Paracrine Signaling To Promote Survival of Human T-Cell Leukemia Virus Type 1-Infected T Cells

“…However, as these early thymocytes progress through stages of differentiation, TrkB expression declines (46). In circulating T cells, it is unclear whether BDNF/TrkB signaling is significant, as either these cells do not express TrkB or its expression is mainly restricted to Th1 cells (47,48). BDNF expression in T cells is similarly disputed and has been analyzed in the context of a direct role played by the immune system in repair of neuronal damage rather than for Tcell survival (47)(48)(49)(50).…”

“…In circulating T cells, it is unclear whether BDNF/TrkB signaling is significant, as either these cells do not express TrkB or its expression is mainly restricted to Th1 cells (47,48). BDNF expression in T cells is similarly disputed and has been analyzed in the context of a direct role played by the immune system in repair of neuronal damage rather than for Tcell survival (47)(48)(49)(50). It is possible that induced BDNF expression is restricted to T-helper subtypes and depends on antigen-mediated activation of these cells (51).…”

SIV infection decreases sympathetic innervation of primate lymph nodes: The role of neurotrophins

“…This raises the possibility that reduced neurotrophin expression following SIV infection might be a consequence of denervation, rather than a cause, since neurotrophins may derive from both immune and neural sources (Kuruvilla, et al, 2004;Bronzetti, et al, 2006;Edling, et al, 2004;Frossard, et al, 2004;Levi-Montalcini, 1987). However, two findings argue against the hypothesis that changes in neurotrophin expression are solely a consequence of denervation.…”

“…Sympathetic neurons express p75 NTR , and TrkA, which binds NGF and NT3 (Reichardt, 2006). BDNF is produced by both sympathetic neurons and target-organ cells including leukocytes (Kuruvilla, et al, 2004;Bronzetti, et al, 2006;Edling, et al, 2004). On sympathetic neurons, which lack Trk B, BDNF acts via p75 NTR to antagonize NGF-mediated support for innervation (Kohn, et al, 1999).…”