T Lymphocytes Activated by Persistent Viral Infection Differentially Modify the Expression of Metalloproteinases and Their Endogenous Inhibitors, TIMPs, in Human Astrocytes: Relevance to HTLV-I-Induced Neurological Disease - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Immunology Année : 2000

T Lymphocytes Activated by Persistent Viral Infection Differentially Modify the Expression of Metalloproteinases and Their Endogenous Inhibitors, TIMPs, in Human Astrocytes: Relevance to HTLV-I-Induced Neurological Disease

Pascale Giraudon
  • Fonction : Auteur
Raphaël Szymocha
Stéphanie Buart
  • Fonction : Auteur
Arlette Bernard
  • Fonction : Auteur
Luis Cartier
  • Fonction : Auteur
Marie-Françoise Belin
  • Fonction : Auteur

Résumé

Activation of T lymphocytes by human pathogens is a key step in the development of immune-mediated neurologic diseases. Because of their ability to invade the CNS and their increased secretion of proinflammatory cytokines, activated CD4+ T cells are thought to play a crucial role in pathogenesis. In the present study, we examined the expression of inflammatory mediators the cytokine-induced metalloproteinases (MMP-2, -3, and -9) and their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMP-1, -2, and -3), in human astrocytes in response to activated T cells. We used a model system of CD4+ T lymphocytes activated by persistent viral infection (human T lymphotropic virus, HTLV-I) in transient contact with human astrocytes. Interaction with T cells resulted in increased production of MMP-3 and active MMP-9 in astrocytes despite increased expression of endogenous inhibitors, TIMP-1 and TIMP-3. These data suggest perturbation of the MMP/TIMP balance. These changes in MMP and TIMP expression were mediated, in part, by soluble factors (presumably cytokines) secreted by activated T cells. Integrin-mediated cell adhesion is also involved in the change in MMP level, since blockade of integrin subunits (alpha1, alpha3, alpha5, and beta1) on T cells resulted in less astrocytic MMP-9-induced expression. Interestingly, in CNS tissues from neurological HTLV-I-infected patients, MMP-9 was detected in neural cells within the perivascular space, which is infiltrated by mononuclear cells. Altogether, these data emphasize the importance of the MMP-TIMP axis in the complex interaction between the CNS and invading immune cells in the context of virally mediated T cell activation.

Dates et versions

hal-03066850 , version 1 (15-12-2020)

Identifiants

Citer

Pascale Giraudon, Raphaël Szymocha, Stéphanie Buart, Arlette Bernard, Luis Cartier, et al.. T Lymphocytes Activated by Persistent Viral Infection Differentially Modify the Expression of Metalloproteinases and Their Endogenous Inhibitors, TIMPs, in Human Astrocytes: Relevance to HTLV-I-Induced Neurological Disease. Journal of Immunology, 2000, 164 (5), pp.2718-2727. ⟨10.4049/jimmunol.164.5.2718⟩. ⟨hal-03066850⟩
8 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More