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Role of CNS-specific “autoregulatory” CD8 T-cells in autoimmune demyelinating disease

Multiple sclerosis (MS) is an inflammatory, demyelinating disorder of the central nervous system (CNS) and is responsible for long-term morbidity in over 350,000 people in the United States. Although the precise etiology of MS is unknown, it is thought to be a T-cell-mediated process due to characteristic histologic features and the presence of neuroantigen-specific immune responses in the blood and cerebrospinal fluid.

MS Relapse CD8 Diagram Preview/Thumbanil

Understanding the immunologic basis of the MS relapse

The most common clinical form of MS presents with a relapsing-remitting course (RRMS). Several immune parameters are different between RRMS patients and healthy subjects, such as imbalance of pro- vs. anti-inflammatory cytokines, chemokine receptor and adhesion molecule changes and deficient CD4 and CD8 Treg function, among others. 

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Genesis of CD4 and CD8 regulatory T cells and effector CD4 T-cell resistance

In addition to dissecting CD8+ T cell-mediated immune regulation, we are also interested in the immune biology of CD4+CD25+FOXP3+ regulatory T cells (T-regs). These cells form an important arm of the immune system responsible for suppressing untoward immune responses.

Diagram showing differential upregulation of immunosuppressive GA-specific CD8+ T-cell responses following GA therapy

Dissecting the immune mechanisms of therapy

An important pursuit in the lab is to understand the immune mechanisms of immunomodulatory therapy.  The goal of these studies is to understand the immune signature of successful therapy to help reveal better therapeutic strategies for the future.

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Clinical test development for MS

Our understanding about the T-cell-mediated immune processes that underlie MS pathogenesis and regulation has improved considerably over the past several years. However, the laboratory tests available for MS do not utilize this advanced level of knowledge.

Diagram showing the role of T-cells in stroke recovery

Adaptive immune cells: Key players in protection and repair following brain injury

The following two projects are led by Sterling B. Ortega, PhD, Associate of Pathology: The role of T-cells in stroke recovery and Brain-targeting adaptive immunity in pediatric Extracorporeal Membrane Oxygenation (ECMO) patients with acquired brain injury.

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SIRPγ: an important checkpoint of human effector T-cells

Signal regulatory protein g (SIRPγ) is uniquely expressed by human T-cells, compared to other immunomodulatory SIRP family members. The role of SIRPγ in T cell function is largely uncharacterized despite accumulating evidence in the literature linking SIRPγ to autoimmune diseases including T1D and SLE.