Medicine and Health Sciences Commons^™

Murine Cmv Infection Induces The Continuous Production Of Mucosal Resident T Cells., Corinne J Smith, Sofia Caldeira-Dantas, Holly Turula, Christopher M. Snyder

Department of Microbiology and Immunology Faculty Papers

Cytomegalovirus (CMV) is a herpesvirus that persists for life and maintains extremely large numbers of T cells with select specificities in circulation. However, it is unknown how viral persistence impacts T cell populations in mucosal sites. We found that many murine (M)CMV-specific CD8s in mucosal tissues became resident memory T cells (TRM). These cells adopted an intraepithelial localization in the salivary gland that correlated with, but did not depend on, expression of the integrin CD103. MCMV-specific TRM cells formed early after infection, and spleen-localized cells had reduced capacities to become TRM at late times. Surprisingly, however, small numbers of new …

Ido2 In Immunomodulation And Autoimmune Disease., George C Prendergast, Richard Metz, Alexander J Muller, Lauren M F Merlo, Laura Mandik-Nayak

Department of Microbiology and Immunology Faculty Papers

IDO2 is a relative of IDO1 implicated in tryptophan catabolism and immune modulation but its specific contributions to normal physiology and pathophysiology are not known. Evolutionary genetic studies suggest that IDO2 has a unique function ancestral to IDO1. In mice, IDO2 gene deletion does not appreciably affect embryonic development or hematopoiesis, but it leads to defects in allergic or autoimmune responses and in the ability of IDO1 to influence the generation of T regulatory cells. Gene expression studies indicate that IDO2 is a basally and more narrowly expressed gene than IDO1 and that IDO2 is uniquely regulated by AhR, which …

Impact Of Distinct Poxvirus Infections On The Specificities And Functionalities Of Cd4+ T Cell Responses., Nicholas A Siciliano, Adam R Hersperger, Aimee M Lacuanan, Ren-Huan Xu, John Sidney, Alessandro Sette, Luis J Sigal, Laurence C. Eisenlohr

Department of Microbiology and Immunology Faculty Papers

UNLABELLED: The factors that determine CD4+ T cell (TCD4+) specificities, functional capacity, and memory persistence in response to complex pathogens remain unclear. We explored these parameters in the C57BL/6 mouse through comparison of two highly related (>92% homology) poxviruses: ectromelia virus (ECTV), a natural mouse pathogen, and vaccinia virus (VACV), a heterologous virus that nevertheless elicits potent immune responses. In addition to elucidating several previously unidentified major histocompatibility complex class II (MHC-II)-restricted epitopes, we observed many qualitative and quantitative differences between the TCD4+ repertoires, including responses not elicited by VACV despite complete sequence conservation. In addition, we observed functional …

Epithelial Immunization Induces Polyfunctional Cd8+ T Cells And Optimal Mousepox Protection., Adam R Hersperger, Nicholas A Siciliano, Brian C Dehaven, Adam E. Snook, Laurence C. Eisenlohr

Department of Microbiology and Immunology Faculty Papers

We assessed several routes of immunization with vaccinia virus (VACV) in protecting mice against ectromelia virus (ECTV). By a wide margin, skin scarification provided the greatest protection. Humoral immunity and resident-memory T cells notwithstanding, several approaches revealed that circulating, memory CD8(+) T cells primed via scarification were functionally superior and conferred enhanced virus control. Immunization via the epithelial route warrants further investigation, as it may also provide enhanced defense against other infectious agents.

Myd88-Dependent Immunity To A Natural Model Of Vaccinia Virus Infection Does Not Involve Toll-Like Receptor 2., Michael L Davies, Janet J Sei, Nicholas A Siciliano, Ren-Huan Xu, Felicia Roscoe, Luis J Sigal, Laurence C. Eisenlohr, Christopher C Norbury

Department of Microbiology and Immunology Faculty Papers

UNLABELLED: Although the pattern recognition receptor Toll-like receptor 2 (TLR2) is typically thought to recognize bacterial components, it has been described to alter the induction of both innate and adaptive immunity to a number of viruses, including vaccinia virus (VACV). However, many pathogens that reportedly encode TLR2 agonists may actually be artifactually contaminated during preparation, possibly with cellular debris or merely with molecules that sensitize cells to be activated by authentic TLR2 agonists. In both humans and mice, the most relevant natural route of infection with VACV is through intradermal infection of the skin. Therefore, we examined the requirement for …

Rip1-Dependent And Independent Effects Of Necrostatin-1 In Necrosis And T Cell Activation., Youngsik Cho, Thomas Mcquade, Haibing Zhang, Jianke Zhang, Francis Ka-Ming Chan

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: Programmed necrosis/necroptosis is an emerging form of cell death that plays important roles in mammalian development and the immune system. The pro-necrotic kinases in the receptor interacting protein (RIP) family are crucial mediators of programmed necrosis. Recent advances in necrosis research have been greatly aided by the identification of chemical inhibitors that block programmed necrosis. Necrostatin-1 (Nec-1) and its derivatives were previously shown to target the pro-necrotic kinase RIP1/RIPK1. The protective effect conferred by Nec-1 and its derivatives in many experimental model systems was often attributed to the inhibition of RIP1 function.

METHODOLOGY/PRINCIPAL FINDINGS: We compared the effect of …

Global Gene Expression Profiling Of Cells Overexpressing Smc3., Giancarlo Ghiselli, Chang-Gong Liu

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: The Structural Maintenance of Chromosome 3 protein (SMC3) plays an essential role during the sister chromatid separation, is involved in DNA repair and recombination and participates in microtubule-mediated intracellular transport. SMC3 is frequently elevated in human colon carcinoma and overexpression of the protein transforms murine NIH3T3 fibroblasts. In order to gain insight into the mechanism of SMC3-mediated tumorigenesis a gene expression profiling was performed on human 293 cells line stably overexpressing SMC3. RESULTS: Biotinylated complementary RNA (cRNA) was used for hybridization of a cDNAmicroarray chip harboring 18,861 65-mer oligos derived from the published dEST sequences. After filtering, the hybridization …