Clinical experimental stroke induces injurious local brain inflammation. However, effects on the peripheral immune system have not been well characterized. We quantified mRNA and protein levels for cytokines, chemokines, chemokine receptors (CCR) in brain, spinal cord, lymphoid organs (spleen, lymph node, blood, cultured mononuclear cells from these sources), blood plasma after reversible middle cerebral artery occlusion (MCAO) or sham treatment male C57BL/6 mice. Middle induced a complex,...

Abstract CD4+CD25+ regulatory T cells are crucial to the maintenance of tolerance in normal individuals. However, factors regulating this cell population and its function largely unknown. Estrogen has been shown protect against development autoimmune disease, yet mechanism is not known. We demonstrate that estrogen (17-β-estradiol, E2) capable augmenting FoxP3 expression vitro vivo. Treatment naive mice with E2 increased both CD25+ number level. Further, ability disease (experimental...

Abstract Induction of stroke not only produces local ischemia and brain damage, but also has profound effects on peripheral immune responses. In the current study, we evaluated spleen blood cells 4 days after induction. Surprisingly, there was a less inflammatory cytokine profile in middle cerebral artery occlusion-affected right hemisphere at 96 h compared with earlier time points. Moreover, our results demonstrate that leads to splenic atrophy characterized by reduction organ size, drastic...

Autoimmune diseases such as multiple sclerosis (MS) may result from the failure of tolerance mechanisms to prevent expansion pathogenic T cells. Our study is first establish that MS patients have abnormalities in FOXP3 message and protein expression levels peripheral CD4+CD25+ cells (Tregs) are quantitatively related a reduction functional suppression induced during suboptimal T-cell receptor (TCR) ligation. Of importance, this observation links defect immunoregulation an established genetic...

Stroke induction in immunologically competent mice not only produces local ischemia and brain damage, but also induces early inflammatory changes peripheral immune responses. Although elements clearly are activated after vascular occlusion, the relative contribution of T B lymphocytes to developing lesion has been quantified. We evaluated effects 22 h middle cerebral artery occlusion (90 mins) on histologic injury activation severe combined immunodeficient (SCID) lacking cells. Cortical...

Evaluation of infarct volumes and infiltrating immune cell populations in mice after middle cerebral artery occlusion (MCAO) strongly implicates a mixture both pathogenic regulatory subsets stroke pathogenesis recovery. Our goal was to evaluate the contribution B cells development MCAO by comparing functional outcomes wild-type (WT) versus B-cell-deficient μMT^−/− mice. The results clearly demonstrate larger volumes, higher mortality, more severe deficits, increased numbers...

Abstract It has been proposed that homeostatic levels of estrogen can enhance female susceptibility to autoimmunity, whereas the heightened associated with pregnancy are protective. This hypothesis was tested using mouse model experimental autoimmune encephalomyelitis (EAE). Diestrus (<100 pg/ml in serum) 17β-estradiol were found significantly reduce clinical manifestations active EAE both male and mice. Estriol also effective but at doses below those previously established for...

Prospects for specific immune intervention in T cell-mediated autoimmune disease via anti-idiotypic regulation depend on the degree of diversity responder cell antigen receptor repertoire. A highly heterogenous response against self epitopes offers little chance such regulation. We report here that Lewis rat experimental allergic encephalomyelitis, generally considered to be a model human multiple sclerosis, is caused by cells use limited set TCR V genes. have cloned alpha and beta chain...

Abstract Adoptive transfer of proteolipid protein 139–151-specific T cell lines was used to examine the role androgens in regulating cytokine secretion and severity experimental autoimmune encephalomyelitis (EAE) SJL mouse. In this study, we found that cells from female mice transferred more severe EAE than male gender differences clinical disease were due, at least part, donor secretion. selected 139–151-immunized presence or absence exogenous androgens. Androgen-selected secreted less...

Multiple sclerosis is an autoimmune disease in which T lymphocytes reactive to myelin basic protein (BP) could play a central role. cells specific for BP were cloned from the blood of multiple patients and normal individuals, expression T-cell receptor variable region genes was analyzed. A remarkable bias use beta-chain (V beta) 5.2 and, lesser extent, V beta 6.1 seen among BP-specific clones but not controls. The preferential recognition did reflect altered this peripheral repertoire....

Estrogen (E2)-induced immunomodulation involves dual effects on antigen-presenting cells (APC) and CD4+CD25+ regulatory T (Treg) but not a direct effect effector cells. In this report, we further investigated the of E2 APC Treg function. We found that treatment in vivo strongly reduced recovery from peritoneal cavity inhibited induction inflammatory cytokines interleukin (IL)-12 interferon-γ enhanced secretion IL-10. Moreover, E2-conditioned bone marrow-derived dendritic (BM-DC) could both...

Estrogen [17-β-estradiol (E2)] is a potent driver of the FoxP3+ regulatory T cell (Treg) compartment. Recently, Tregs were further characterized by intracellular expression negative co-stimulatory molecule, programmed death-1 (PD-1). To clarify role PD-1 versus FoxP3 in E2-enhanced Treg suppression, we evaluated both markers and functional suppression wild-type, estrogen receptor knockout (ERKO) mice KO mice. We demonstrate that also E2 sensitive, since treatment increased levels CD4+FoxP3+...

Encephalitogenic T cells specific for myelin basic protein share common V β 8 peptide sequences in their cell receptor (TCR) that can induce autoregulatory and antibodies prevent clinical signs of experimental autoimmune encephalomyelitis (EAE). It is not known, however, if TCR peptides treat established disease. To test its therapeutic value, TCR-V 8-39-59 was injected into rats with EAE. This treatment reduced disease severity speeded recovery, apparently by boosting anti-V raised...

The mechanisms by which prolonged estrogen exposures, such as therapy and pregnancy, reduce thymus weight, cellularity, CD4 CD8 phenotype expression, have not been well defined. In this study, the roles played membrane receptor, G protein-coupled receptor 30 (GPR30), intracellular receptors, alpha (ERalpha) beta (ERbeta), in 17beta-estradiol (E2)-induced thymic atrophy were distinguished construction side-by-side comparison of GPR30-deficient mice with ERalpha ERbeta gene-deficient mice. Our...

Abstract CD4 + CD25 regulatory T cells (Treg cells) prevent cell‐mediated autoimmune diseases in rodents. To develop a functional Treg assay for human blood cells, we used FACS‐ or bead‐sorted from healthy donors to inhibit anti‐CD3/CD28 activation of − indicator cells. The data clearly demonstrated classical suppression by both +high and +low obtained FACS magnetic bead sorting. Suppressive activity was found either CD45RO (naive) (memory) subpopulations, independent the TCR signal...

Colony-stimulating activities (CSA) are potent granulopoietic stimulators in vitro. Using clonogenic assay techniques, we analyzed the degree to which mononuclear phagocytes and T lymphocytes cooperate positive (production/release of CSA) feedback (inhibition CSA production/release) regulation granulopoiesis. We measured effect lactoferrin (a putative regulator production) on provision three separate systems wherein granulocyte colony growth marrow cells from 22 normal volunteers was...

Although estrogens exert a pronounced protective effect on multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), their therapeutic application has been limited by undesirable side effects thought to be mediated primarily through estradiol binding intracellular estrogen receptor alpha. In this study, we found that signaling the putative membrane receptor, G protein-coupled 30 (GPR30), was sufficient mediate protection against EAE, which significantly...