Intrinsic IL-2 production by effector CD8 T cells affects IL-2 signaling and promotes fate decisions, stemness, and protection.

Here, we show that the capacity to manufacture IL-2 identifies constituents of the expanded CD8 T cell effector pool that display stem-like features, preferentially survive, rapidly attain memory traits, resist exhaustion, and control chronic viral challenges. The cell-intrinsic synthesis of IL-2 by CD8 T cells attenuates the ability to receive IL-2-dependent STAT5 signals, thereby limiting terminal effector formation, endowing the IL-2-producing effector subset with superior protective powers. In contrast, the non-IL-2-producing effector cells respond to IL-2 signals and gain effector traits at the expense of memory formation.

Predicting the Probability of Chlamydia Reinfection in African American Women Using Immunologic and Genetic Determinants in a Bayesian Model.

Background: African Americans have the highest rates of Chlamydia trachomatis (CT) infection in the United States and also high reinfection rates. The primary objective of this study was to develop a Bayesian model to predict the probability of CT reinfection in African American women using immunogenetic data.

Methods: We analyzed data from a cohort of CT-infected African American women enrolled at the time they returned to a clinic in Birmingham, AL, for the treatment of a positive routine CT test result.

An Adaptive -Specific IFN-γ-Producing CD4 T Cell Response Is Associated With Protection Against Chlamydia Reinfection in Women.

Adaptive immune responses that mediate protection against (CT) remain poorly defined in humans. Animal chlamydia models have demonstrated that CD4 Th1 cytokine responses mediate protective immunity against reinfection. To better understand protective immunity to CT in humans, we investigated whether select CT-specific CD4 Th1 and CD8 T cell cytokine responses were associated with protection against CT reinfection in women.

Stimulated peripheral blood mononuclear cells from chlamydia-infected women release predominantly Th1-polarizing cytokines.

Chlamydia trachomatis infection (chlamydia) is the most prevalent sexually transmitted bacterial infection and causes significant reproductive morbidity in women. Little is known about how immunity to chlamydia develops in women, though animal models of chlamydia indicate that T-helper type 1 (Th1) responses are important for chlamydia clearance and protective immunity, whereas T-helper type 2 (Th2) responses are associated with persisting infection. In chlamydia-infected women, whether the predominant immune response is Th1- or Th2-polarizing remains controversial.

Performance of Chlamydia trachomatis OmcB Enzyme-Linked Immunosorbent Assay in Serodiagnosis of Chlamydia trachomatis Infection in Women.

serological assays with improved sensitivity over commercially available assays are needed to evaluate the burden of infection and the effectiveness of prevention efforts. We evaluated the performance of a outer membrane complex protein B (OmcB) enzyme-linked immunosorbent assay (ELISA) in the detection of anti- antibody responses in -infected women. OmcB ELISA was less sensitive than our elementary body (EB) ELISA, but it was highly specific.

T cell phenotypes in women with Chlamydia trachomatis infection and influence of treatment on phenotype distributions.

T cell phenotypes involved in the immune response to Chlamydia trachomatis (CT) have not been fully elucidated in humans. We evaluated differences in T cell phenotypes between CT-infected women and CT-seronegative controls and investigated changes in T cell phenotype distributions after CT treatment and their association with reinfection. We found a higher expression of T cell activation markers (CD38HLA-DR), T helper type 1 (Th1)- and Th2-associated effector phenotypes (CXCR3CCR5 and CCR4, respectively), and T cell homing marker (CCR7) for both CD4 and CD8 T cells in CT-infected women.

Distinct peripheral vs mucosal T-cell phenotypes in chlamydia-infected women.

Problem: Differences in circulating (peripheral) and mucosal T-cell phenotypes in chlamydia-infected women remain largely unknown.

Method Of Study: Thirteen paired mononuclear cell specimens from blood and cervicovaginal lavages collected from chlamydia-infected women were stained and analyzed using ten-color cell surface flow cytometry for T-cell distribution, activation status, homing, and T helper (Th)-associated chemokine receptors (CKRs).

Results: A higher proportion of genital mucosal T-cells were activated (CD38 HLA-DR ) and expressed CCR5 and Th1-associated CKR CXCR3 CCR5 compared to peripheral T-cells, but a lower proportion of mucosal T-cells expressed homing CKR CCR7, Th-2 associated CKR CCR4, and CXCR3 CCR4 for both T-cell subsets.

Lower Levels of Cervicovaginal Tryptophan Are Associated With Natural Clearance of Chlamydia in Women.

Chlamydiatrachomatis (Ct) infection causes significant morbidity. In vitro studies demonstrate that Ct growth inhibition occurs by interferon-gamma (IFN-γ)-mediated depletion of intracellular tryptophan, and some Ct strains utilize extracellular indole to restore tryptophan levels. Whether tryptophan levels are associated with Ct infection clearance in humans remains unknown.

Immunoglobulin-Based Investigation of Spontaneous Resolution of Chlamydia trachomatis Infection.

Chlamydia trachomatis elementary body enzyme-linked immunosorbent assay (ELISA) was used to investigate serum anti-CT immunoglobulin G1 (IgG1; long-lived response) and immunoglobulin G3 (IgG3; short-lived response indicating more recent infection) from treatment (enrollment) and 6-month follow-up visits in 77 women previously classified as having spontaneous resolution of chlamydia. Of these women, 71.4% were IgG1+IgG3+, consistent with more recent chlamydia resolution.

The Predominant CD4 Th1 Cytokine Elicited to Chlamydia trachomatis Infection in Women Is Tumor Necrosis Factor Alpha and Not Interferon Gamma.

infection is the most prevalent bacterial sexually transmitted infection and can cause significant reproductive morbidity in women. There is insufficient knowledge of -specific immune responses in humans, which could be important in guiding vaccine development efforts. In contrast, murine models have clearly demonstrated the essential role of T helper type 1 (Th1) cells, especially interferon gamma (IFN-γ)-producing CD4 T cells, in protective immunity to chlamydia.

A Context-Dependent Role for IL-21 in Modulating the Differentiation, Distribution, and Abundance of Effector and Memory CD8 T Cell Subsets.

The activation of naive CD8 T cells typically results in the formation of effector cells (TE) as well as phenotypically distinct memory cells that are retained over time. Memory CD8 T cells can be further subdivided into central memory, effector memory (TEM), and tissue-resident memory (TRM) subsets, which cooperate to confer immunological protection. Using mixed bone marrow chimeras and adoptive transfer studies in which CD8 T cells either do or do not express IL-21R, we discovered that under homeostatic or lymphopenic conditions IL-21 acts directly on CD8 T cells to favor the accumulation of TE/TEM populations.

Optimized Replicating Renilla Luciferase Reporter HIV-1 Utilizing Novel Internal Ribosome Entry Site Elements for Native Nef Expression and Function.

We previously developed replication-competent reporter HIV-1 (referred to herein as LucR.T2A reporter viruses), utilizing a "ribosome skipping" T2A peptide strategy to link Renilla luciferase (LucR) with Nef expression. The demonstrated utility for HIV-1 vaccine and transmission study applications included measurement of neutralizing antibody (NAb) activity in vaccine sera, improved cell-mediated virus inhibition assays, such as T cell-mediated virus inhibition and antibody-dependent cell-mediated cytotoxicity (ADCC) assays, and humanized mouse models.

Frequency, Private Specificity, and Cross-Reactivity of Preexisting Hepatitis C Virus (HCV)-Specific CD8+ T Cells in HCV-Seronegative Individuals: Implications for Vaccine Responses.

Unlabelled: T cell responses play a critical role in controlling or clearing viruses. Therefore, strategies to prevent or treat infections include boosting T cell responses. T cells specific for various pathogens have been reported in unexposed individuals and an influence of such cells on the response toward vaccines is conceivable.

Role of a cirrhosis risk score for the early prediction of fibrosis progression in hepatitis C patients with minimal liver disease.

Background & Aims: Fibrosis progression in patients with chronic hepatitis C (CHC) is highly variable. A Cirrhosis Risk Score (CRS) based on seven genetic variants has been recently developed for identifying patients at risk for cirrhosis. The objective of this study was to assess the role of the CRS for the early prediction of fibrosis progression in CHC patients with mild liver fibrosis.

Monocytes transduced with lentiviral vectors expressing hepatitis C virus non-structural proteins and differentiated into dendritic cells stimulate multi-antigenic CD8(+) T cell responses.

Halting the spread of hepatitis C virus (HCV) and also eradicating HCV in subjects with chronic infection are major goals for global health. To this end, several years of research on HCV vaccine development have led to the conclusion that multi-antigenic and multi-functional vaccine types are necessary for effectiveness against HCV infection. In this study, we evaluated lentiviral vectors (LV) expressing clusters of HCV structural (LV-HCV-S) and non-structural (LV-HCV-NS) genes for future vaccine development.