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K Pfizenmaier

Publications and source records attributed to K Pfizenmaier.

At least 145 records · Page 8Linked to original sources
PubMed1980

Intrathymic differentiation of cytotoxic T lymphocyte (CTL) precursors. I. The CTL immunocompetence of peanut agglutinin-positive (cortical) and negative (medullary) Lyt 123 thymocytes.

To analyze the developmental and functional interrelationship between cortical and medullary thymocytes, the peanut agglutinin-(PNA) binding capacity was used to separate thymocytes into PNA+ (cortical) and PNA- (medullary) thymocytes. Virtually, all positively selected PNA+ thymocytes (90% of the overall thymocyte population) expressed the Lyt 123 phenotype, whereas 90% of negatively selected PNA- thymocytes expressed Lyt 1 alloantigens, about 10% being Lyt 123 thymocytes. Provided, the requirement of Lyt 1 T helper cells was bypassed by Interleukin 2, a nonspecific mediator of T help, PNA+ Lyt 123 thymocytes mounted cytotoxic T cell responses comparable in magnitude to that of peripheral T cells. Their repertoire included antigenic disparities coded for by the complete MHC complex, H-2K, I-A, H-2D, mutational events at H-2K, as well as antigenic disparities expressed on TNP conjugated- and Sendai virus-infected syngeneic cells. PNA- Lyt 123 thymocytes represent a highly reactive pool of primary cytotoxic T lymphocyte (CTL) precursors for both alloreactive and H-2-restricted CTL responses. Since PNA- thymocytes include also Lyt 1 T helper cells, PNA- responder thymocytes are able to mount autonomously (CTL responses. Our data are first to provide direct evidence that Lyt 123 cells represent a common source of alloreactive and H-2-restricted CTL precursors in unprimed lymphocyte populations. Moreover, the apparent immunocompetence of cortical PNA+ thymocytes is now explained by their lack of T helper cells.

Agglutinins↗
PubMed1978

Primary in vitro sensitization of virus specific cytotoxic T lymphocytes.

CBA mouse-derived splenic lymphocytes treated with either beta-priopionlactone-inactivated or u.v. light-inactivated parainfluenza (sendai) virus stimulated in vitro unprimed syngeneic T-lymphocytes to differentiate into cytotoxic T-lymphocytes (CTL). The CTL generated were virus specific and H-2 restricted. For optimal CTL responses to be induced (i) a critical treatment of stimulator cells, (ii) an optimal ratio of responder to stimulator cells and (iii) an in vitro incubation period of 5 days was required. The in vitro system for the induction of primary virus-specific CTL responses may be useful to analyse the sensitization phase of H-2 restricted virus-specific CTL.

Animals↗
PubMed1977

Cyclophosphamide-sensitive T lymphocytes suppress the in vivo generation of antigen-specific cytotoxic T lymphocytes.

Murine T lymphocytes sensitized in vitro against either allogeneic lymphocytes or syngeneic hapten-conjugated lymphocytes do differentiate into highly effective cytotoxic T lymphocytes (CTL) (1-3). In vivo immunization of T lymphocytes to the same antigens, however, results in the generation of only marginal cytotoxic activity (1,4,5). Recently we found that the weakness of in vivo generated cytotoxicity is not due to a failure of antigen-induced T-cell sensitization but rather due to suppression of the in vivo differentiation of sensitized CTL precursors into effective CTL(6). In keeping with this finding it was postulated that suppressor cells may regulate the in vivo differentiation of CTL. We now report, that cyclophosphamide-sensitive T cells suppress the in vivo differentiation of antigen-specific CTL. Thus, pretreatment of mice with a single dose of cyclophosphamide (100 mg/kg) converts their state of low responsiveness to a state of high responsiveness.

Animals↗
PubMed1977

Generation of cytotoxic T lymphocytes against Ly alloantigen.

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).

Alleles↗
PubMed1977

Virion antigens introduced exogeneously into the cell membrane render syngeneic target cells susceptible for T cell-mediated cytolysis.

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.

Animals↗
PubMed1977

The role of T cells in anti-herpes simplex virus immunity. I. Induction of antigen-specific cytotoxic T lymphocytes.

Mice infected with herpes simplex virus develop little or no cytotoxic T lymphocyte (CTL) response. However, in lymph nodes (LN's) draining a local site infected with HSV, antigen-specific CTL precursors are sensitized, which upon transfer to in vitro culture conditions develop within 72 hr into effective CTL. The in vivo blockade of CTL differentiation can be overcome by cyclophosphamide, suggesting that a cyclophosphamide-sensitive mechanism blocks the in vivo generation of HSV-immune CTL. The cytolytic activity of HSV-immune CTL is H-2 restricted and antigen specific. Thus CTL sensitized toward HSV type 1 discriminate between syngeneic targets infected with either the immunologic HSV variant type 1 or type 2 (and vice versa). H-2-matched target cells exposed for 30 min to infectious HSV are lysed within 60 min of contact with CTL. Since HSV replication is believed to require more than 4 to 5 hr, the data suggest that either the expression of HSV-dependent "early proteins" takes place within 30 to 90 min or cell membrane-integrated HSV virion represents the target antigen of CTL.

Animals↗
PubMed1976

Virus and trinitrophenol hapten-specific T-cell-mediated cytotoxicity against H-2 incompatible target cells.

Immune spleen cells from LCM virus-infected (CBA X C57BL/6)F1 radiation chimeras entirely repopulated with CBA-T6 lymphocytes were cytotoxic for allogeneic, LCM virus infected C57BL/6 mouse-derived target cells. Normal C57BL/6 targets were not lysed. CBA-T6 lymphocytes derived from (CBA X C57BL/6) radiation chimeras sensitized in vitro against TNP-conjugated C57BL/6 spleen cells lysed TNP-conjugated C57BL/6 targets. However normal C57BL/6 mouse-derived targets were not destroyed. The magnitude of virus-specific (or TNP-specific) cytotoxic responses against H-2 incompatible targets was lower compared to that against H-2 compatible targets. These data are considered to support and to extend the altered self concept, but are not consistent with the dual recognition concept.

Animals↗
PubMed1976

Shared determinants between virus-infected and trinitrophenyl-conjugated H-2-identical target cells detected in cell-mediated lympholysis.

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 determinants can be detected on either LCM virus-infected and TNP-conjugated targets, which are not present on the cell surface of normal target cells.

Animals↗
PubMed1976

In vivo sensitization of T cells to hapten-conjugated syngeneic structures of major histocompatibility complex. I. Effect of in vitro culture upon generation of cytotoxic T lymphocytes.

Murine T cells were sensitized in vitro towards fluorescein isothiocyanate (FITC)-conjugated syngeneic spleen cells. The lytic activity of the effector cells generated was restricted to FITC-conjugated, H-2-compatible target cells. 2,4,6-Trinitrophenyl (TNP)-conjugated syngeneic targets were not lysed. A method is described for the in vivo sensitization of murine T cells towards TNP (or FITC)-conjugated syngeneic spleen cells. The procedure is based on the observation that a local graft of hapten-conjugated syngeneic spleen cells results in the development of sensitized prekiller T cells within the draining lymph node (LN). By mere in vitro incubation of such LN cells immunological specific anti-TNP (or anti-FITC)-reactive cytotoxic T lymphocytes (CTL) are generated. The in vitro differentiation of CTL requires 48-72 h; it is dependent on cell proliferation and is abolished by treatment of the LN cells with mitomycin C. Thus there is a separation between the sensitization of CTL precursors (which effectively takes place in vivo) and the phase of cell differentiation into CTL (which effectively takes place only in vitro). Similar to in vitro-sensitized CTL, the specificity of in vivo-sensitized CTL is dictated by the hapten used for the induction of the immune response and is restricted to hapten-conjugated syngeneic target cells.

Animals↗
PubMed1976

Cell-mediated immunity to H-2 antigens. Characteristics of the effector cells as detected in the microcytotoxicity assay.

Cell-mediated immune reactivity against murine histocompatibility antigens was compared by using both the microcytotoxicity assay (MCA) and the 51 chromium release assay (CRA). In both assay systems the data obtained showed T cell-mediated reactivity. In the CRA only T lymphocytes were detectable, which were cytotoxic, In contrast, in the MCA reactivity of nonlytic secondary T cells (NLST) was also detected. NLST acquired their MCA-reactivity within the first 24 hr of the 48-hr test period of the MCA. Circumstantial evidence is provided suggesting that MCA reactivity is a product of two different processes, namely, antigen-specific restimulation of immunt T cells and shedding of cytotoxicity inhibiting factors.

Animals↗