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K Winkel

Publications and source records attributed to K Winkel.

16 recordsLinked to original sources
PubMed1997

Dendritic cells and T lymphocytes: developmental and functional interactions.

Dendritic cells (DCs) are specialized for presentation of antigen to T cells and are essential for primary T cell activation. Although DCs are generally considered to be myeloid derived, we now have evidence that a subgroup are of lymphoid origin. In particular, the DCs of the adult mouse thymus appear to be derived from the same early, lymphoid-restricted precursor cells that generate T lymphocytes. Purified early thymic T precursors have the capacity to produce T cells, B cells, NK cells and DCs, but not myeloid cells, on transfer to irradiated recipients. They also produce thymic DCs on culture with a mix of cytokines; this mix does not include GM-CSF, needed to generate myeloid-derived DCs. A subgroup of DCs in other lymphoid organs, which like thymic DCs express CD8 as an alpha alpha homodimer, may likewise be of lymphoid origin. These CD8+ DCs in mouse spleen differ functionally from the conventional CD8+ DCs. CD8+ DCs efficiently activate CD4+ T cells but then kill them via Fas ligand on the DC surface. CD8+ DCs efficiently recruit CD8+ T cells into the cell cycle, but their proliferation is then restricted by an inadequate production of interleukin 2. This subgroup of CD8+ DCs therefore appears to have a regulatory role.

Animals↗
PubMed1997

Are CD8+ dendritic cells (DC) veto cells? The role of CD8 on DC in DC development and in the regulation of CD4 and CD8 T cell responses.

The CD8-expressing dendritic cells (DC) present in mouse spleen have been shown to have a regulatory effect on the CD4 and CD8 T cells they activate, restricting subsequent T cell proliferation by either inducing apoptotic T cell death (CD4 T cells) or by limiting endogenous cytokine production (CD8 T cells). To determine the role of the CD8 molecule itself in these regulatory phenomena, the DC from CD8 null mice were studied. The DC marker DEC-205 (NLDC 145) was used as a surrogate marker for CD8, since the expression of these two molecules on splenic DC was closely correlated. DC levels were normal, and the incidence of DEC-205+ and DEC-205- DC was normal in CD8 null mice, indicating that the absence of CD8 did not affect DC development. The proliferative response of T cells to allogeneic DEC-205+ DC from either CD8-/- or CD8+/+ mice was similar and was much less than the response to DEC-205- DC from these mice. This applied to both the CD4 and the CD8 T cell responses. Thus the lack of the CD8 molecule did not affect the stimulatory or regulatory properties of the DC. The regulatory CD8+ DEC-205+ DC therefore differ in that respect from antigen-presenting 'veto' cells, where CD8 itself is involved in transmitting negative signals to the T cells. DEC-205 may prove to be a more pertinent marker of the regulatory DC population.

Animals↗
PubMed1996

A subclass of dendritic cells regulates the response of naive CD8 T cells by limiting their IL-2 production.

Previous work indicated that a subclass of mouse spleen dendritic cells (DC), those bearing CD8alpha, expresses the Fas ligand and restricts peripheral CD4 T cell responses by initiating Fas-mediated apoptosis. To determine whether a similar regulation applies to CD8 T cells, they were purified from normal or from TCR-transgenic mice, and then cultured with purified splenic CD8+ DC or CD8- DC presenting either alloantigens or the specific Ag for the TCR transgene. In all systems studied, the proliferative response of CD8 T cells was markedly less on stimulation with CD8+ DC compared with conventional CD8- DC. However, the basis of this restricted proliferation in response to CD8+ DC was totally different for CD8 T cells than for CD4 T cells. The reduced proliferation of CD8 T cells occurred later in the response than with CD4 T cells. In contrast with CD4 T cells, the reduced proliferation of CD8 T cells occurred even with T cells from Fas-deficient Ipr mice, or with DC from Fas ligand-deficient gld mice, indicating that Fas-induced apoptosis was not involved. Also, in contrast with CD4 T cells, the reduced proliferation of CD8 T cells was completely reversed by the addition of exogenous IL-2. Furthermore, cultures of CD8 T cells with CD8+ DC were found to be deficient in IL-2 production. Accordingly, although CD8+ DC are very efficient at stimulating CD8 T cells into cell division, they are deficient at stimulating endogenous cytokine production. The implications of these different DC regulatory systems are discussed.

Animals↗
PubMed1995

Mouse thymus dendritic cells: kinetics of development and changes in surface markers during maturation.

The early thymus precursor population of adult mice has the capacity to generate T cells, B cells and dendritic cells (DC). These precursors were injected into the thymus of irradiated recipients in order to follow the kinetics of thymic DC development. The resultant cohort of T-lineage cells developing in the thymus was accompanied by a parallel cohort of DC, present at 10(3)-fold lower frequency. The intrathymic lifespan of these DC was as short as that of T-lineage thymocytes. As the thymic DC matured, some markers characteristic of the original precursor population gradually declined (Ly-5, c-kit, Sca-2) whereas markers characteristic of thymic DC appeared and were maintained (major histocompatibility complex class II, CD11c, NLDC-145 and CD8 alpha). Some thymic DC expressed the early B-cell marker BP-1, and BP-1 mRNA, throughout their maturation. The surface markers on thymic DC could be divided into two groups. Some markers, including class I and class II MHC, CD8 alpha and BP-1, appeared to be integral components of the DC surface. In contrast, other markers, including Thy-1, CD4 and CD8 beta, had probably been picked up from associated thymocytes.

Animals↗
PubMed1994

CD4 and CD8 expression by human and mouse thymic dendritic cells.

Dendritic cells (DC) from human and mouse thymus were compared. DC from both sources were isolated by digestion with collagenase, disruption of cellular complexes with a chelating agent, selection of light density cells, immunomagnetic bead depletion of other cell types (without depletion with anti-CD4 or anti-CD8) and finally sorting for cells expressing high levels of class II MHC. Yields of DC from human and mouse thymus were comparable (around 1 DC/10(3) thymocytes), they displayed similar DC morphology, and both showed strong expression of CD11c. DC from the human thymus all expressed very high levels of CD4 but low levels of CD8. In contrast, DC from the mouse thymus expressed high levels of CD8 but only low levels of CD4. Human thymic DC were also substantially larger than mouse thymic DC. The biological significance of CD4 and CD8 expression by DC is discussed in view of this major species difference and the possibility that human thymic DC may be targets for HIV infection.

Animals↗
PubMed1986

Neutrophil function in localized juvenile periodontitis. Phagocytosis, superoxide production and specific granule release.

Patients with localized juvenile periodontitis (LJP) exhibit defective neutrophil functions to a variety of environmental and host stimuli. It is not clear, however, how many of the measurable functions are defective and whether individual patients exhibit single or multiple dysfunctions. The purpose of this study was to evaluate chemotaxis, phagocytosis, specific granule release and superoxide production in a group of 23 previously unreported LJP patients. Our results indicate that all 23 of these LJP patients exhibited chemotaxis depression to N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) and endotoxin-activated serum (EAS). Smaller groups from the 23 chemotactically defective LJP group were used to test other function due to inability to obtain sufficient quantities of blood. Fourteen of 14 LJP patients tested exhibited defective phagocytosis. Ten LJP patients were evaluated for specific granule release, and 14 LJP patients were evaluated for superoxide production. Both granule release and superoxide production were found to be normal in chemotactically defective LJP patients. Since both defective and normal responses noted in the same neutrophil populations are mediated by the same receptor, it is hypothesized that the cellular defect lies in a post receptor pathway.

Aggressive Periodontitis↗