A5026429291- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- melanin and skin pigmentation
- CAR-T cell therapy research
- Atherosclerosis and Cardiovascular Diseases
- Systemic Lupus Erythematosus Research
- Hepatitis C virus research
- Monoclonal and Polyclonal Antibodies Research
- Skin Protection and Aging
- Histiocytic Disorders and Treatments
- Chemokine receptors and signaling
- Liver Disease Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Tuberous Sclerosis Complex Research
- Heat shock proteins research
- Cytomegalovirus and herpesvirus research
- Vascular Tumors and Angiosarcomas
- Advanced Glycation End Products research
- Diabetes and associated disorders
- Cell Adhesion Molecules Research
- Immune cells in cancer
- Immune Response and Inflammation
- vaccines and immunoinformatics approaches
- Hepatitis B Virus Studies
University of Colorado Anschutz Medical Campus
2020-2025
University of Colorado Denver
2006-2025
University of Cincinnati Medical Center
2012-2020
Cincinnati Children's Hospital Medical Center
2012-2020
Bipar
2018
Loyola University Chicago
2008-2016
Loyola University Medical Center
2012-2016
University of Cincinnati
2014-2016
Children’s Institute
2016
Oncology Hematology Care
2012
Infection with hepatitis C virus (HCV) is associated persistence in the majority of individuals. We demonstrate here that inhibitory molecule programmed death-1 (PD-1) significantly upregulated on total and HCV-specific CD8(+) cytotoxic T lymphocytes (CTLs) peripheral blood livers patients chronic infection compared to subjects spontaneous HCV resolution, nonviral liver disease, normal controls. PD-1 expression cytomegalovirus-specific CTLs also varies according status highest infection. are...
Background. Acute hepatitis C virus (HCV) infection is often asymptomatic; thus, its epidemiology and natural history are difficult to define.
Adaptive immune responses to Ags released by dying cells play a critical role in the development of autoimmunity, allograft rejection, and spontaneous as well therapy-induced tumor rejection. Although cell death these situations is considered sterile, various reports have implicated type I IFNs drivers ensuing adaptive response cell-associated Ags. However, mechanisms that underpin this IFN production are poorly defined. In article, we show dendritic (DCs) can uptake sense nuclear...
In human vitiligo, cutaneous depigmentation involves cytotoxic activity of autoreactive T cells. It was hypothesized that can progress in the absence regulatory cells (Treg). The percentage Treg among skin infiltrating evaluated by immunoenzymatic double staining for CD3 and FoxP3, revealing drastically reduced numbers non-lesional, perilesional lesional vitiligo skin. Assessment circulating pool FACS analysis CD4, CD25, CD127 FoxP3 expression, mixed lymphocyte reactions presence sorted...
Interleukin-7 (IL-7) is required for the establishment and maintenance of memory CD4+ CD8+ T lymphocytes, cells lacking IL-7Rα (CD127) demonstrate impaired IL-2 secretion have a short life-span. Chronic HCV characterized by that are functionally exhibit an immature phenotype. To investigate potential role IL-7/IL-7Rα in outcome infection, we used multiparameter flow cytometry to characterize patients with acute infection (n = 24), long-term chronic (12) normal subjects (13). per se resulted...
Up-regulation of programmed death-1 (PD-1) identifies exhausted T cells in various mouse and human viral models including chronic hepatitis C virus (HCV) infection, which is characterized by impaired CTL function. A large proportion patients fail to eradicate HCV with current IFN-based antiviral therapy; particular, African Americans are less likely respond, but the mechanisms for these differences not fully elucidated. In this study, 72 treatment-naive persistent we found that PD-1 was...
HSP70i and other stress proteins have been used in anti-tumor vaccines. This begs the question whether plays a unique role immune activation. We vaccinated inducible (Hsp70-1) knockout mice wild-type animals with optimized TRP-1, highly immunogenic melanosomal target molecule. were unable to induce robust lasting depigmentation Hsp70-1 mice, vivo cytolytic assays revealed lack of cytotoxic T-lymphocyte activity. Absence T-cell infiltration skin maintenance hair follicle melanocytes observed....
Abstract Lysophosphatidic acid (LPA) is a bioactive lipid which increases in concentration locally and systemically across different cancer types. Yet, the exact mechanism(s) of how LPA affects CD8 T cell immunosurveillance during tumor progression remain unknown. We show receptor (LPAR) signaling by cells promotes tolerogenic states via metabolic reprogramming potentiating exhaustive-like differentiation to modulate anti-tumor immunity. found levels predict response immunotherapy Lpar5...
Infection with hepatitis C virus (HCV) is characterized by impairment of viral effector T cell responses and a high propensity for persistence. Previous studies have demonstrated that chronic HCV infection associated an increased frequency regulatory (T(reg)) cells, compared in persons whose resolved healthy persons. However, all patients prior analyses had exposures the distant past, precluding ability to determine whether T(reg) cells play causal role establishing persistence during...
ABSTRACT The mechanisms mediating protective immunity to hepatitis C virus (HCV) infection are incompletely understood because early in humans is rarely identified, particularly those individuals who subsequently demonstrate spontaneous eradication. We have established a large national network of patients with acute HCV infection. Here, we comprehensively examined total HCV-specific CD4 + and CD8 T-cell responses identified functional thresholds that predict recovery. Interestingly, found...
Inducible HSP70 (HSP70i) chaperones peptides from stressed cells, protecting them apoptosis. Upon extracellular release, HSP70i serves an adjuvant function, enhancing immune responses to bound peptides. We questioned whether differentially protects control and vitiligo melanocytes stress subsequent responses. compared expression of in skin samples, evaluated the viability primary exposed bleaching phenols, measured secreted HSP70i. determined traffics melanosomes contact immunogenic proteins...
The relationship between B cells and CD4 T has been carefully studied, revealing a collaborative effort in which promote the activation, differentiation, expansion of while so-called "helper" provide signals to cells, influencing their class switching fate. Interactions CD8 are not as well although exhibit an accelerated contraction after certain infections B-cell-deficient mice. Here, we find that significantly enhance primary cell responses vaccination. Moreover, memory numbers function...
Abstract Recent advancements in T cell immunotherapy suggest that cells engineered with high-affinity TCR can offer better tumor regression. However, whether a alone is sufficient to control growth, or the subset bearing also important remains unclear. Using human tyrosinase epitope-reactive, CD8-independent, isolated from MHC class I-restricted CD4+ obtained tumor-infiltrating lymphocytes (TIL) of metastatic melanoma patient, we developed novel transgenic mouse C57BL/6 background. This...
T regulatory cells (Treg) avert autoimmunity, but their increased levels in melanoma confer a poor prognosis. To explore the basis for Treg accumulation melanoma, we evaluated chemokine expression patients. A 5-fold increase was documented chemoattractants CCL22 and CCL1 melanoma-affected skin versus unaffected skin, as accompanied by infiltrating FoxP3+ cells. In parallel, there an approximately two-fold enhancement of CCR4 circulating not effector We hypothesized that redirecting away from...
T cell responses to subunit vaccination require both IL-27 and IL-15 support an aerobic glycolysis–independent metabolic program.
Eya proteins are critical developmental regulators that highly expressed in embryogenesis but downregulated after development. Amplification and/or re-expression of Eyas occurs many tumor types. In breast cancer, regulate progression by acting as transcriptional cofactors and tyrosine phosphatases. Intriguingly, harbor a separate threonine (Thr) phosphatase activity, which was previously implicated innate immunity. Here we describe what believe to be novel role for Eya3 mediating...
Abstract Objectives While much of the research concerning factors associated with responses to immune checkpoint inhibitors (ICIs) has focussed on contributions conventional peptide‐specific T cells, role unconventional such as mucosal‐associated invariant (MAIT) in human melanoma remains largely unknown. MAIT cells are an abundant population innate‐like expressing a semi‐invariant T‐cell receptor restricted MHC class I‐like molecule, MR1, presenting vitamin B metabolites derived from...
The presence of B cells is essential for the formation CD8 T cell memory after infection and vaccination. In this study, we investigated whether influence programming naïve prior to their involvement in an immune response. RNA sequencing indicated that are necessary sustaining FOXO1-controlled transcriptional program, which critical homeostasis. Without appropriate repertoire, mouse exhibit a terminal, effector-skewed phenotype, significantly impacts response A similar phenotype with reduced...
Hepatitis C virus (HCV) infection is a leading cause of chronic hepatitis, end-stage liver disease, and hepatocellular carcinoma throughout the world. Considerable evidence indicates that risk viral persistence, natural history, response to antiviral therapy varies among racial groups, but limited data exist on potential mechanisms account for these differences. Type 1 helper (Th1) responses HCV proteins cytomegalovirus (CMV) antigens were examined using sensitive interferon (IFN)-gamma...