Human T cells show plasticity for direct recognition of xenogeneic dendritic cells.

Organ shortage continues to be the forefront of problems facing clinical transplantation. Although xenografts serve as a promising alternative, its success is contingent upon further investigation into the mechanisms of cell-mediated xenograft rejection. Here, we explored the direct and indirect contribution of human immune cells in xenorecognition using human and murine in vitro coculture systems.

TLR3 and TLR7/8 agonists improve immunization outcome in nicotine exposed mice through different mechanisms.

It is known that cigarette smoke compromises the immune system and increases the risk of vaccine-preventable diseases. We reported that nicotine, the immunosuppressive component of cigarette smoke, disrupts the functional properties of DC and DC crosstalk with NK cells, which is pivotal in the initiation of immune responses to vaccines. We also showed that select TLR agonists could reduce the degrading effects of nicotine on DC-NK mediated immune responses in vitro.

Combination of TLR8 and TLR4 agonists reduces the degrading effects of nicotine on DC-NK mediated effector T cell generation.

The magnitude of immune responses to vaccination is a critical factor in determining protection from disease. It is known that cigarette smoke dampens the immune system and increases the risk of vaccine-preventable diseases. We reported that nicotine, the immunosuppressive component of cigarette smoke, disrupts the differentiation and functional properties of DC, which are pivotal in the initiation of immune response to vaccines.

TLR8 combined withTLR3 or TLR4 agonists enhances DC-NK driven effector Tc1 cells.

Background: Most current prophylactic vaccines confer protection primarily through humoral immunity. Indeed, aluminum salts which have been widely used as adjuvants in vaccines primarily enhance Th2-driven antibody responses. Therefore, new vaccines formulation is moving toward a careful selection of adjuvants that also elicit significant Th1 or Tc1 responses.

Restricting Glutamine or Glutamine-Dependent Purine and Pyrimidine Syntheses Promotes Human T Cells with High FOXP3 Expression and Regulatory Properties.

T cell subsets differ in their metabolic requirements, and further insight into such differences might be harnessed to selectively promote regulatory T cells (Tregs) for therapies in autoimmunity and transplantation. We found that Gln restriction during human T cell activation favored CD4 T cells with high expression of the Treg transcription factor FOXP3. This resulted from shrinking numbers and reduced proliferation of activated FOXP3(lo/-)CD4 T cells while FOXP3(hi)CD4 T cell numbers increased.

Exposure to nicotine adversely affects the dendritic cell system and compromises host response to vaccination.

The magnitude of Th1 cells response to vaccination is a critical factor in determining protection from clinical disease. Our previous in vitro studies suggested that exposure to the nicotine component of cigarette smoke skews the differentiation of both human and mouse dendritic cell (DC) precursors into atypical DCs (DCs differentiated ex vivo in the presence of nicotine) lacking parameters essential for the development of Th1-mediated immunity. In this study, we determined the causal relationship between nicotine-induced DC alterations and host response to vaccines.

Chitin particles induce size-dependent but carbohydrate-independent innate eosinophilia.

Murine Mϕ that phagocytose CMP develop into M1; this response depends on the size and the chemical composition of the particles. In contrast, recent studies concluded that chitin particles induce M2 and eosinophil migration, promoting acquired Th2 immune responses against chitin-containing microbes or allergens. This study examined whether these apparently inconsistent responses to chitin could be induced by variation in the size and chemical composition of the chitin particles.

Comparative analysis of dendritic cells and anti-CD3/CD28 expanded regulatory T cells for application in transplantation.

The containment of direct and indirect recognition of donor alloantigens by enhancement of the number and activity of regulatory T cells (Tregs) has been one of the promising approaches to achieve transplant tolerance. Two major methods, dendritic cell (DC) and anti-CD3/CD28 antibodies (Abs) have been introduced for ex vivo expansion of Tregs prior to their adoptive transfer. Here we compared the clinical advantage of using these methods of Tregs expansion by evaluating the nature and ability of expanded Tregs to abolish recipient alloreactive T-cell responses in vitro and in vivo.

B7-1 and B7-2 differentially control peripheral homeostasis of CD4(+)CD25(+)Foxp3(+) regulatory T cells.

Targeting the CD28/B7 interaction remains among the most promising approaches to treat transplant rejection. A drawback to this approach is however the observations of decreased numbers of naturally occurring regulatory T cells (Tregs) in CD28(-) or B7-deficient non-obese diabetic (NOD) mice, cells that maintain immunological self tolerance, prevent autoimmunity and control immune responses to transplants. In this study, therefore, we investigated the relative contributions of B7-1 and B7-2, the only known ligands of CD28, on the thymic development and peripheral homeostasis of Tregs.

A possible mechanism linking cigarette smoke to higher incidence of respiratory infection and asthma.

T helper type 1 (Th1) cells are responsible for cell-mediated immunity against invading pathogens, while Th2 cells provide help to B cells and control allergic responses. The polarization of naïve Th cells into Th1 or Th2 subsets is controlled by dendritic cells (DCs) migrating from the periphery to draining lymph nodes. Migrating DCs carry not only antigen-specific 'signal 1' and costimulatory 'signal 2', but also Th-polarizing 'signal 3' that reflects the nature of the pathogen and the character of the infected tissue.

Nicotinic environment affects the differentiation and functional maturation of monocytes derived dendritic cells (DCs).

Differentiation of tissue monocytes into DCs is a critical phase in the development of a competent immune system. We show that in a nicotinic environment, while human monocytes differentiate into DCs (henceforth called nicDCs) with a typical morphology, they display unique phenotype and cytokine profile that adversely affect their function. Despite an increased capacity for receptor-dependent antigen uptake, nicDCs do not express CD1a and fail to fully up-regulate MHCs, molecules essential for their antigen-presenting function.

Evidence for the immunosuppressive role of nicotine on human dendritic cell functions.

Nicotine alters a wide range of immunological functions, including innate and adaptive immune responses. To date, no studies have been reported showing the immunoregulatory effects of nicotine on dendritic cells (DCs), which are critical cells for initiation of cell-mediated immunity against infection and neoplastic diseases. In this work, we report that, in a nicotinic environment, monocyte-derived DCs manifest lower endocytic and phagocytic activities.

Direct and indirect cross-tolerance of alloreactive T cells by dendritic cells retained in the immature stage.

Background: Rejection of allografts entails the direct and indirect cross-recognition of donor major histocompatibility complex molecules by recipient alloreactive T cells. The ability to manipulate the state of dendritic cell (DC) maturation in vitro has enabled us to induce tolerance specifically targeting the alloreactive T-cell compartment. In this study, the immunoregulatory effect of alloantigen presentation by ex vivo-generated donor and recipient DCs retained in immature stage was investigated.