0000000000150467
AUTHOR
Klaus Pfizenmaier
showing 18 related works from this author
Protein Kinase C μ Is Regulated by the Multifunctional Chaperon Protein p32
2000
We identified the multifunctional chaperon protein p32 as a protein kinase C (PKC)-binding protein interacting with PKCalpha, PKCzeta, PKCdelta, and PKC mu. We have analyzed the interaction of PKC mu with p32 in detail, and we show here in vivo association of PKC mu, as revealed from yeast two-hybrid analysis, precipitation assays using glutathione S-transferase fusion proteins, and reciprocal coimmunoprecipitation. In SKW 6.4 cells, PKC mu is constitutively associated with p32 at mitochondrial membranes, evident from colocalization with cytochrome c. p32 interacts with PKC mu in a compartment-specific manner, as it can be coimmunoprecipitated mainly from the particulate and not from the so…
T-cell-derived helper factor allows in vivo induction of cytotoxic T cells in nu/nu mice
1980
T-cell immunocompetence and diversity are thought to be generated in the thymus1,2. This view is based on the findings that (1) T-cell ontogeny is thymus dependent3,4, (2) the major histocompatibility restrictions of T-cell interactions are phenotypically related to the H–2 type of the thymus5–9, and (3) the phenotypic manifestation of H–2-linked immune responsiveness parallels the restriction elements selected in thymus10–12. However, it is unclear whether pre-thymic cells programmed to develop into T cells do already express a receptor diversity, also whether pre-thymic cells have the potential to react against self-antigens, and whether the mechanism of self-tolerance is initiated in the…
Generation of Cytotoxic T Lymphocytes Against Ly Alloantigen
2008
Cytotoxic T lymphocytes specific for immune alloantigens controlled by alleles of the Ly system have been induced in vivo. These results were obtained either in a secondary type of response or by treating mice before immunization with a single dose of cyclophosphamide (80 mg/kg).
Shared determinants between virus-infected and trinitrophenyl-conjugated H-2-identical target cells detected in cell-mediated lympholysis
1976
Infection of H-2-identical mice with either lymphocytic choriomeningitis (LCM) virus, vaccinia virus, or paramyxo (Sendai) virus resulted in the generation of specifically sensitized cytotoxic T lymphocytes (CTL). CTL generated in vitro against 2,4,6-trinitrophenyl (TNP)-conjugated syngeneic stimulator cells were specifically cytotoxic for TNP-conjugated H-2K (D) region identical targets. Both LCM and vaccinia-induced CTL, however, were found to be strongly cytotoxic towards TNP-conjugated, H-2K(D) region-identical target cells. In contrast, Sendai virus-induced CTL did not lyse TNP-conjugated, syngeneic target cells. Inhibition experiments using cold targets suggested that shared antigenic…
Herpes-Simplex-virus-specific, H-2Dk-restricted T lymphocytes bear receptors for H-2Dd alloantigen.
1980
Cytotoxic T lymphocytes generated in the course of an HSV-infection of CBA (H-2k) mice not only lyse syngeneic, virus-infected target cells but also cross-react with noninfected taraget cells expressing the Dd alloantigen. On the effector cell level, this alloreactivity is mediated by virus-specific CTL's that are restricted to H-2Dk determinants. On the prekiller cell level, the anti-HSV-reactive T cells exhibiting cross-reactivity for Dd alloantigen could be positively selected on H-2d spleen-cell monolayers. After differentiation into cytolytic effector cells, target cells expressing Dd alloantigens and syngeneic HSV-infected target were lysed with equal efficiency. The results imply tha…
Frequency-Analysis of Precursors of Cytotoxic T Lymphocytes in Radiation Chimeras: Enumeration of Antigenspecific CTL-P Restricted to Thymic MHC- and…
1984
The mechanisms controlling the acquisition of T cell restriction specificity and immunocompetence are, despite of numerous investigations, not well understood. From studies of the CTL-immune responsiveness in thymus- and bone marrow-grafted chimeric mice, it became apparent, that it is the thymus which is crucial not only for the maturation or T cells, but also for the specificity repertoire of the T cells (1,2). From these data it was suggested, that during intra-thymic maturation both mutational events and positive selection mechanisms influence the repertoire such that only T cells restricted to thymic epithelial cell MHC determinants mature and will be exported to the peripheral lymphoi…
Tailoring the stealth properties of biocompatible polysaccharide nanocontainers.
2014
Fundamental development of a biocompatible and degradable nanocarrier platform based on hydroxyethyl starch (HES) is reported. HES is a derivative of starch and possesses both high biocompatibility and improved stability against enzymatic degradation; it is used to prepare nanocapsules via the polyaddition reaction at the interface of water nanodroplets dispersed in an organic miniemulsion. The synthesized hollow nanocapsules can be loaded with hydrophilic guests in its aqueous core, tuned in size, chemically functionalized in various pathways, and show high shelf life stability. The surface of the HES nanocapsules is further functionalized with poly(ethylene glycol) via different chemistri…
Virion Antigens Introduced Exogeneously into the Cell Membrane Render Syngeneic Target Cells Susceptible for T Cell-Mediated Cytolysis
1977
Non-infectious sendai virus renders H-2 matched target cells susceptible to the lytic effect of sendai virus immune cytotoxic T lymphocytes. This observation suggests that exogeneous insertion of virion antigen in the membrane of the target cell is sufficient for T cell cytotoxicity. The finding is incompatible with the concept that H-2K or H-2D gene products of the target cells must be altered in their primary structure (pretranslational effect of the virus infection) for T cell-mediated cytolysis to occur.
The in Vivo Effects of Interleukin 2 (TCGF)
1982
This brief review of our experiments concerning the in vivo activity of crude Il-2 led us to the following conclusion: The first is the existence, in vivo, of a cyclophosphamide-sensitive T-cell controlling the activity of a serum born Il-2 inhibitor in thymus-bearing normal mice. Under in vivo conditions which are characterized by high Il-2 inhibitor activities, locally applied Il-2 administered along with antigen amplified in vivo CTL-responsiveness, yet the effect observed was poor. Crude Il-2 proved to be a potent immuno-enhancing agent in the athymic (nu/nu) mouse, which lacks Il-2 inhibitor activity. It was found that together with antigen administration of Il-2 to nude mice results i…
Anti H-2Dd alloreactivity mediated by herpes-simplex-virus specific cytotoxic H-2k T lymphocytes is associated with H-2Dk.
1980
Herpes-simplex-virus (HSV) specific, H-2k-restricted, immune cytotoxic T lymphocytes also lyse noninfected H-2d target cells. Genetic mapping studies revealed that HSV-specific Dk-restricted CTL cross-react with allogeneic targets expressing Dd alloantigens. Cold target inhibition experiments indicate that only a minority of HSV-specific CTL mediate cross-reactive cytolysis. The data give an example of where the phenomenon of H-2-restricted versus nonrestricted responsiveness is not due to distinct subsets of T cells but solely depends on the antigenic determinants recognized.
Functional Analysis of Alloreactive Helper T Cells Involved in the Induction of Cytolytic T Cell Responses In Vitro
1984
When T-responder cells are sensitized in vitro to foreign antigen presented on syngeneic cells or towards allogeneic stimulator cells, a proliferative response is initiated in which antigen specific cytotoxic T lymphocytes (CTL) are generated. The induction of CTL, however, requires the collaboration between functionally distinct T cell subpopulations1–5 and accessory cells from the macrophage lineage, including dendritic cells. The experimental data accumulated so far reveal a cascade of T-T cell interactions and distinct functions of their soluble products resulting in the “Interleukin concept”6 (Fig. 1). Upon receptor-antigen interaction, the “antigen-selected” clones of CTLp become sens…
T-cell-mediated cytotoxicity against herpes simplex virus-infected target cells
1977
THE control of herpes simplex virus (HSV) infection by immunological mechanisms seems to be complex and is poorly understood. Neutralising antibodies to HSV plus complement seem to have no effect on the propagation of HSV infection, because HSV spreads to adjacent cells by passing through intercellular bridges1–3. Anti-HSV antibodies plus complement, however, destroy virus-infected cells, but cannot prevent the spread of HSV, suggesting that the virus must be transferred to neighbouring cells before immune lysis occurs1,5. Therefore if lymphocyte-mediated cytolytic mechanisms are instrumental in blocking the spread of HSV in vivo, they ought to destroy infected cells at a very early stage i…
T-T cell collaboration during in vivo responses to antigens coded by the peripheral and central region of the MHC.
1976
MIXED lymphocyte culture (MLC)1 has been used extensively as an in vitro model to analyse the reactivity of T cells to antigens coded by the major histocompatibility complex (MHC). When murine T responder cells are exposed in vitro to allogeneic lymphoid cells (stimulator cells) they proliferate and cytotoxic T lymphocytes (CTL) are generated2,3. Antigens coded by the central I region of the MHC are chiefly responsible for triggering proliferation4,5, whereas the target antigen of the CTL generated is either a H–2K or H–2D region or a I–A subregion gene product5–8. This dichotomy in the antigenic requirement of a MLC seems to be reflected at the level of the responding T lymphocytes. Two di…
T-T cell interactions during in vitro cytotoxic T lymphocyte responses. III. Antigen-specific T helper cells release nonspecific mediator(s) able to …
1980
T helper cell induction and the specificity of T cell-mediated help as generated during alloreactive and H-2-restricted, virus- or hapten-specific cytotoxic T lymphocyte (CTL) responses have been compared. With the use of a double-chamber culture system, it was possible to dissect and separately analyze the induction phase of T helper cells from the T helper cell effector function. The data obtained revealed that during alloreactive as well as H-2-restricted T cell responses, antigen-specific T helper cells are induced. Upon specific restimulation of T helper cells, helper cell function is mediated across a cell-impermeable membrane via soluble products in an apparently nonspecific and nonr…
T-T cell interactions during cytotoxic T cell responses. IV. Murine lymphoid dendritic cells are powerful stimulators for helper T lymphocytes.
1982
Enriched populations of Ia+ Fc receptor-negative dendritic cells were compared to other cell types for their stimulatory activity in primary mixed lymphocyte reactions to alloantigens and 2,4,6,-trinitrophenylated syngeneic cells. Dendritic cells were 20-100 times more effective than unfractionated splenocytes. A second cell type exhibiting strong stimulatory activity was an Ia+ Fc receptor-positive transiently adherent cell. Both types of stimulatory cells were only effective when able to produce the monokine interleukin 1. Thus glutaraldehyde-fixed cells were not stimulatory unless extraneous interleukin 1 was added. Stimulation of helper cells by either dendritic cells or Ia+ Fc receptor…
Alloreactive and H-2-restricted Lyt 23 cytotoxic T lymphocytes derive from a common pool of antecedent Lyt 123 precursors.
1980
If the collaborative requirement of Lyt 1 T helper cells is bypassed by the Lyt 1 T cell-derived mediator of T help, termed Il-2, upon antigenic stimulation, PNA+ Lyt 123 thymocytes differentiate into either alloreactive or H-2-restricted PNA- Lyt 23 cytotoxic effector cells. Along the differentiation pathway from Lyt 123 leads to 23 effector cells, cytolytic activity is carried out by T cells that still express the Lyt 123 phenotype. The data establish that Lyt 23 CTL are produced by differentiation from antecedent Lyt 123 cells.
T-cell-derived helper factor allows Lyt 123 thymocytes to differentiate into cytotoxic T lymphocytes.
1979
IT is generally accepted that the diversity of T-cell responsiveness is generated in the thymus1. It is also known that except for a few Lyt 1 cells all thymocytes express the Lyt 123 phenotype2,3. Surprisingly, thymocytes are poorly responsive in vitro4, and only the medullary thymocytes, comprising 5–10% of the total thymic cell population, show an in vitro responsiveness comparable with that of peripheral T cells5. Cortical thymocytes, comprising 90–95% of all thymocytes, have previously been considered to be immature and immunologically incompetent4. The result reported here show that thymocytes are able to generate alloantigen-, virus- and hapten-specific cytotoxic T lymphocytes (CTL),…
The Role of the Major Histocompatibility Gene Complex in Murine Cytotoxic T Cell Responses
1980
Publisher Summary An interpretation of the function of major histocompatibility complex (MHC) in cytotoxic T cell responses requires making certain assumptions, which, because of the lack of experimental data, are often based on intuition. This chapter discusses some specific aspects of the role of MHC in cytotoxic T cell responses. It also summarizes the expression of T cell-mediated responses to alloantigens. It also focuses on H-2-restricted cytotoxic T lymphocytes (CTL) responses and discusses the influence of the MHC on cytotoxic T cell specificity and CTL responsiveness against foreign antigens. T cell responses to alloantigens mirror all the functional activities seen in H-2-restrict…