Correlation between susceptibility to demyelination and interferon-γ induction of major histocompatibility complex class II antigens on murine cerebrovascular endothelial cells

Welsh, Jane; Sapatino, B. V.; Rosenbaum, B.; Smith, Roger; Linthicum, Scott

doi:10.1016/0165-5728(93)90062-4

Cited by 30 publications

(13 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A correlation also has been found between IFN-g-induced MHC class II expression on CVE and susceptibility to demyelination in the TVID model. (26) In the present study, we have demonstrated the ability of IFN-t to downregulate IFN-g-induced MHC class II on CVE derived from TVID-susceptible mice. Downregulation of MHC class II might result in the reduction of antigen presentation and a subsequent reduction in inflammation.…”

Section: Discussionmentioning

confidence: 79%

See 1 more Smart Citation

Ovine IFN-τModulates the Expression of MHC Antigens on Murine Cerebrovascular Endothelial Cells and Inhibits Replication of Theiler's Virus

Tennakoon

Smith²,

Stewart³

et al. 2001

Journal of Interferon & Cytokine Research

View full text Add to dashboard Cite

Interferon-beta (IFN-beta) has been used successfully to treat patients with relapsing-remitting multiple sclerosis (MS). IFN-tau is a new class of type I IFN that is secreted by the trophoblast and is the signal for maternal recognition of pregnancy in sheep. IFN-tau has potent immunosuppressive and antiviral activities similar to other type I IFN but is less cytotoxic than IFN-alpha/beta. The current investigation concerns the effect of recombinant ovine IFN-tau (rOvIFN-tau) on the modulation of MHC class I and II expression on cloned mouse cerebrovascular endothelial (CVE) cells. IFN-tau induced tyrosine phosphorylation of Stat1 and upregulated the expression of MHC class I on CVE. One proposed action by which type I IFN reduce the relapse rate in MS is via interference with IFN-gamma-induced MHC class II expression. IFN-tau was shown to downregulate IFN-gamma-induced MHC class II expression on CVE and, hence, may be of potential therapeutic value in downregulating inflammation in the central nervous system (CNS). IFN-tau did not upregulate the expression of MHC class II on CVE. IFN-tau also inhibited the replication of Theiler's virus in CVE. These in vitro results suggest that IFN-tau may be of therapeutic value in the treatment of virus-induced demyelinating disease.

show abstract

Section: Discussionmentioning

confidence: 79%

“…BALB/c CVE cells fail to express MHC class II following treatment with IFN-g, as previously shown. (26) …”

Section: Ifn-t Fails To Upregulate the Expression Of Mhc Class II On Cvementioning

confidence: 97%

Ovine IFN-τModulates the Expression of MHC Antigens on Murine Cerebrovascular Endothelial Cells and Inhibits Replication of Theiler's Virus

Tennakoon

Smith²,

Stewart³

et al. 2001

Journal of Interferon & Cytokine Research

View full text Add to dashboard Cite

show abstract

“…Interestingly, the ability of CVEs to up-regulate MHC class II on the cell surface in response to IFN-␥ in mice is strain dependent and may correspond to susceptibility to EAE. 26,27 Welsh et al 27 have reported the up-regulation of MHC class II on CVEs from EAE-susceptible SJL/J mice, but not on CVEs from EAE-resistant BALB/c mice. However, other cytokines, including TNF-␣, may also play a role in the regulation of MHC class II on endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…27 Briefly, brains were removed from 2-to 4-week-old SJL/J mice, and the meninges and macroscopic pial vessels were removed by dissection. Brains were transferred to a second Petri dish, and the tissue was minced.…”

Section: Cerebrovascular Endothelial Cell Isolationmentioning

confidence: 99%

“…It has been demonstrated that IFN-␥-treated endothelial cells, including those comprising the CNS microvasculature, can express many of the cell surface molecules, including MHC class II molecules, required for T-cell activation. 24,25 Moreover, the ability of CVEs to up-regulate the expression of MHC class II molecules appears to correlate with susceptibility to EAE in mouse and rat species, 26,27 despite evidence that MHC compatibility between CVEs and encephalitogenic T cells is not required for the induction of EAE. [28][29][30][31][32][33] It has been hypothesized that the disparate results reported to date may be attributed to the level of contamination of primary endothelial cell cultures with so-called professional APCs.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Differential abilities of central nervous system resident endothelial cells and astrocytes to serve as inducible antigen-presenting cells

Girvin

Gordon

Welsh

et al. 2002

Blood

View full text Add to dashboard Cite

IntroductionThe brain has been considered an immune-privileged site in the presence of an intact blood-brain barrier (BBB). The BBB consists of tight junctions between cerebrovascular endothelial cells (CVEs), and it serves as a physical barrier limiting T-cell and antibody passage into the central nervous system (CNS). 1 Few unactivated T cells are capable of extravasating through the BBB, regardless of their antigen specificity, but low numbers of T cells can be found in the CNS of healthy humans and rats, so there appears to be a role for T-cell surveillance of the CNS in the absence of inflammation. Under these conditions, the low expression of major histocompatibility complex (MHC) class II and T-cell costimulation/adhesion molecules on CNS-resident cells renders the CNS an unsuitable site for T-cell priming. However, during an inflammatory immune response, the BBB is disrupted and all T cells and mononuclear cells have the ability to traffic into the brain and spinal cord and to recognize target antigens within the CNS. [2][3][4] Under these conditions, potential antigen-presenting cells (APCs) residing in the CNS are likely to play a major role in T-cell responses and may contribute to the propagation or regulation of inflammatory immune responses in the CNS, as they do in multiple sclerosis (MS).The BBB is damaged by demyelinating diseases such as MS and its animal model, experimental autoimmune encephalomyelitis (EAE). MS and EAE are characterized by CNS infiltration of myelin protein-specific Th1 cells, pro-inflammatory cytokine production of interferon-␥ (IFN-␥) and tumor necrosis factor-␣ (TNF-␣), mononuclear cell accumulation, and destruction of myelin. 5,6 CNS-resident cells, particularly microglia, pericytes, astrocytes, and CVEs, have the potential to affect the immune response by serving as APCs in the target organ. To serve as an APC, a cell must be able to express the requisite molecules to deliver the 2 signals necessary to activate a T cell. 7 Signal 1 is the antigen-specific signal delivered by antigen in MHC class II binding to the T-cell receptor (TCR). Signal 2, the costimulatory signal, is potently delivered by the B7 family of molecules binding to CD28 on the surface of the T cell. 8 Other costimulatory/adhesion molecules (ie, CD40, CD152, CD106) can deliver or enhance signal 2. 9-11 Professional APCs, such as B lymphocytes, macrophages, and dendritic cells, have been reported to constitutively express MHC class II and B7-1/2. Nonprofessional APCs must up-regulate MHC class II and B7 family members in response to an inflammatory stimulus. The class II transactivator (CIITA), which is absent in the human disease bare-lymphocyte syndrome, 12 has been found to be essential for the inducible and constitutive expression of MHC class II, 13,14 and it is the master switch for MHC class II expression. Moreover, the CIITA has a significant effect on the expression of other proteins associated with class II antigen processing and presentation, including H-2M and invariant chain (Ii). 15 CIITA pr...

show abstract

Differential reactivity of brain microvascular endothelial cells to TNF reflects the genetic susceptibility to cerebral malaria

et al. 1998

View full text Add to dashboard Cite

Upon infection with Plasmodium berghei ANKA (PbA), various inbred strains of mice exhibit different susceptibility to the development of cerebral malaria (CM). Tumor necrosis factor-§ (TNF) and interferon-+ (IFN-+) have been shown to be crucial mediators in the pathogenesis of this neurovascular complication. Brain microvascular endothelial cells (MVEC) represent an important target of both cytokines. In the present study, we show that brain MVEC purified from CM-susceptible (CM-S) CBA/J mice and CM-resistant (CM-R) BALB/c mice exhibit a different sensitivity to TNF. CBA/J brain MVEC displayed a higher capacity to produce IL-6 and to up-regulate intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in response to TNF than BALB/c brain MVEC. In contrast, no difference was found in the induction of E-selectin after TNF challenge. CM-S brain MVEC were also significantly more sensitive to TNF-induced lysis. This differential reactivity to TNF was further substantiated by comparing TNF receptor expression on CM-S and CM-R brain MVEC. Although the constitutive expression of TNF receptors was comparable on cells from the two origins, TNF induced an up-regulation of both p55 and p75 TNF receptors in CM-S, but not in CM-R brain MVEC. A similar regulation was found at the level of TNF receptor mRNA, but not for receptor shedding. Although a protein kinase C inhibitor blocked the response to TNF in both the brain MVEC, an inhibitor of protein kinase A selectively abolished the response to TNF in CM-R, but not CM-S brain MVEC, suggesting a differential protein kinase involvement in TNF-induced activation of CM-S and CM-R brain MVEC. These results indicate that brain MVEC purified from CM-S and CM-R mice exhibit distinctive sensitivity to TNF. This difference may be partly due to a differential regulation of TNF receptors and via distinct protein kinase pathways.

show abstract

Correlation between susceptibility to demyelination and interferon-γ induction of major histocompatibility complex class II antigens on murine cerebrovascular endothelial cells

Cited by 30 publications

References 19 publications

Ovine IFN-τModulates the Expression of MHC Antigens on Murine Cerebrovascular Endothelial Cells and Inhibits Replication of Theiler's Virus

Ovine IFN-τModulates the Expression of MHC Antigens on Murine Cerebrovascular Endothelial Cells and Inhibits Replication of Theiler's Virus

Differential abilities of central nervous system resident endothelial cells and astrocytes to serve as inducible antigen-presenting cells

Differential reactivity of brain microvascular endothelial cells to TNF reflects the genetic susceptibility to cerebral malaria

Contact Info

Product

Resources

About