Mucosal-Associated Invariant T cells exhibit distinct functional signatures associated with protection against typhoid fever.

We have previously demonstrated that Mucosal-Associated Invariant T (MAIT) cells secrete multiple cytokines after exposure to Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever in humans. However, whether cytokine secreting MAIT cells can enhance or attenuate the clinical severity of bacterial infections remain debatable.

Human Typhi exposure generates differential multifunctional cross-reactive T-cell memory responses against Paratyphi and invasive nontyphoidal .

Objective: There are no vaccines for most of the major invasive strains causing severe infection in humans. We evaluated the specificity of adaptive T memory cell responses generated after Typhi exposure in humans against other major invasive strains sharing capacity for dissemination.

Methods: T memory cells from eleven volunteers who underwent controlled oral challenge with .

Challenge of Humans with Wild-type Serovar Typhi Elicits Changes in the Activation and Homing Characteristics of Mucosal-Associated Invariant T Cells.

Gastrointestinal infections by serovar Typhi (. Typhi) are rare in industrialized countries. However, they remain a major public health problem in the developing world with an estimated 26.

Importance of Typhi-Responsive CD8+ T Cell Immunity in a Human Typhoid Fever Challenge Model.

Typhoid fever, caused by the human-restricted organism serovar Typhi (. Typhi), constitutes a major global health problem. The development of improved attenuated vaccines is pressing, but delayed by the lack of appropriate preclinical models.

Cross-reactive multifunctional CD4+ T cell responses against Salmonella enterica serovars Typhi, Paratyphi A and Paratyphi B in humans following immunization with live oral typhoid vaccine Ty21a.

The live oral typhoid vaccine Ty21a elicits predominantly CD8+, as well as CD4+ T cells mediated immune responses. Clinical field studies showed that Ty21a is moderately effective against S. Typhi and S.

Salmonella Typhi-specific multifunctional CD8+ T cells play a dominant role in protection from typhoid fever in humans.

Background: Typhoid fever, caused by the human-restricted organism Salmonella Typhi (S. Typhi), is a major public health problem worldwide. Development of novel vaccines remains imperative, but is hampered by an incomplete understanding of the immune responses that correlate with protection.

Oral Wild-Type Salmonella Typhi Challenge Induces Activation of Circulating Monocytes and Dendritic Cells in Individuals Who Develop Typhoid Disease.

A new human oral challenge model with wild-type Salmonella Typhi (S. Typhi) was recently developed. In this model, ingestion of 104 CFU of Salmonella resulted in 65% of subjects developing typhoid fever (referred here as typhoid diagnosis -TD-) 5-10 days post-challenge.

Activation of Salmonella Typhi-specific regulatory T cells in typhoid disease in a wild-type S. Typhi challenge model.

Salmonella Typhi (S. Typhi), the causative agent of typhoid fever, causes significant morbidity and mortality worldwide. Currently available vaccines are moderately efficacious, and identification of immunological responses associated with protection or disease will facilitate the development of improved vaccines.

Bone marrow vaccination: a novel approach to enhance antigen specific antitumor immunity.

Bone marrow (BM) serves as a reservoir for a unique population of memory T cells with strong effector properties that make them ideal targets for cancer immunotherapy strategies. However, direct vaccination and priming of T cells within the BM of the host has never been investigated. This study evaluates the specific immune response induced via a new method of direct intra-bone marrow (IBM) vaccination in an animal model of human papillomavirus-associated cancer.

Association of mixed hematopoietic chimerism with elevated circulating autoantibodies and chronic graft-versus-host disease occurrence.

Background: Use of a reduced-intensity conditioning regimen before an allogeneic hematopoietic cell transplantation is frequently associated with an early state of mixed hematopoietic chimerism. Such a coexistence of both host and donor hematopoietic cells may influence posttransplant alloreactivity and may affect the occurrence and severity of acute and chronic graft-versus-host disease (GVHD) as well as the intensity of the graft-versus-leukemia effect. Here we evaluated the relation between chimerism state after reduced-intensity conditioning transplantation (RICT), autoantibody production, and chronic GVHD (cGVHD)-related pathology.

Can tolerogenic dendritic cells help to modulate allo-immune responses in the setting of hematopoietic cell transplantation?

Recent evidence suggests that recipient as well as donor dendritic cell (DC) subsets are implicated in hematopoietic engraftment, graft-vs.-host disease occurrence, immune reconstitution and graft-vs.-leukemia effects observed after allogeneic hematopoietic cell transplantation.

Polybrene and interleukin-4: two opposing factors for retroviral transduction of bone-marrow-derived dendritic cells.

Background: Gene transfer using retroviral transduction offers the advantage of long-term transgene expression in developing strategies that use dendritic cells (DCs) for immunotherapy. The goal of this study was to infect DCs in an immature state in order to take advantage of their proliferating and tolerogenic potential.

Methods: Immature DCs were generated from murine bone marrow (BM) using either GM-CSF alone or GM-CSF plus IL-4.

Exposure to exogenous DNA can modify the sensitivity of the Fas apoptotic pathway.

Background: Gene-transfer techniques are commonly employed for both in vitro and in vivo studies. However, modifications of the target cell following the introduction of the gene of interest are not often examined. These modifications can alter the immunogenicity and/or the susceptibility of the target cell to apoptosis and may produce unwanted consequences in vivo.