Semaphorin CD100 from activated T lymphocytes induces process extension collapse in oligodendrocytes and death of immature neural cells.
An inappropriate cross talk between activated T lymphocytes infiltrating the CNS and neural cells can sustain the onset and progression of demyelination and axonal degeneration in neuroinflammatory diseases. To mimic this deleterious cross talk, we designed an experimental paradigm consisting of transient cocultures of T lymphocytes chronically activated by retrovirus infection (not virus productive) with human multipotent neural precursors or primary oligodendrocytes from rat brain. We showed that activated T lymphocytes induced apoptotic death of multipotent neural progenitors and immature oligodendrocytes after a progressive collapse of their process extensions. These effects were reminiscent of those induced by brain semaphorin on neural cells. Blockade by specific Abs of soluble CD100 (sCD100)/semaphorin 4D released by activated T cells, or treatment with rsCD100, demonstrated that this immune semaphorin has the ability to collapse oligodendrocyte process extensions and to trigger neural cell apoptosis, most likely through receptors of the plexin family. The specific presence of sCD100 in the cerebrospinal fluid and of CD100-expressing T lymphocytes in the spinal cord of patients suffering with neuroinflammatory demyelination pointed to the potential pathological effect of sCD100 in the CNS. Thus, our results show that CD100 is a new important element in the deleterious T cell-neural cell cross talk during neuroinflammation and suggest its role in demyelination or absence of remyelination in neuroinflammatory diseases including multiple sclerosis and human T lymphotropic virus type 1-associated myelopathy.
Giraudon
Pascale
P
INSERM Unit 433, Experimental Neurobiology and Physiopathology, Federative Institut of Neuroscience 19, Faculty of Medicine R Laennec, rue G. Paradin, 69372 Lyon CEDEX 08, France. giraudon@lyon.inserm.fr
Vincent
Peggy
P
Vuaillat
Carine
C
Verlaeten
Olivier
O
Cartier
Luis
L
Marie-Cardine
Anne
A
Mutin
Mireille
M
Bensussan
Armand
A
Belin
Marie-Françoise
MF
Boumsell
Laurence
L
D000328:Adult; D000368:Aged; D000818:Animals; D015703:Antigens, CD; D017209:Apoptosis / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000502:physiology; D009474:Neurons / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D009836:Oligodendroglia / Q000276:immunology / Q000473:pathology*; D015493:Paraparesis, Tropical Spastic / Q000276:immunology* / Q000473:pathology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000502:physiology; D039961:Semaphorins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D012995:Solubility; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; C093224:CD100 antigen; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C492119:PLXNB1 protein, human; D011956:Receptors, Cell Surface; D039961:Semaphorins