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Biomedical subjects

M Röllinghoff

Publications and source records attributed to M Röllinghoff.

At least 199 records · Page 11Linked to original sources
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

Induction of I region-restricted hapten-specific cytotoxic T lymphocytes.

Murine cytotoxic T lymphocytes (CTL) reactive to TNP-conjugated syngeneic target cells do lyse to a moderate but significant extent TNP-conjugated, I region compatible but H-2K or H-2D region incompatible target cells. Antibody inhibition experiments and "cold inhibition" experiments indicate that some CTL clones recognize TNP-conjugated targets in association with syngeneic I region determinants independently of H-2K or H-2D gene products. The data suggest that besides TNP-conjugated H-2K or H-2D gene products, in principle, also TNP-conjugated I region determinants do stimulate TNP-specific CTL precursor cells and act as target antigens of TNP-specific CTL.

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

Secondary cytotoxic allograft responses in vitro. II. Differentiation of memory T cells into cytotoxic T lymphocytes in the absence of cell proliferation.

Murine cytotoxic T lymphocytes (CTL) were induced in "one-way" mixed lymphocyte cultures and their physical characteristics investigated by velocity sedimentation at 1 X g. The in vitro differentiation of progenitors of CTL into primary and secondary CTL was paralleled by characteristic changes in the size of the responder cells. Fractionated cells enriched for primary blast CTL reverted into clonally restricted "nonlytic" secondary T lymphocytes. Upon antigenic reexposure, these lymphocytes differentiated into secondary CTL within 18-32 h. This took place in the absence of cell proliferation and could be triggered by UV light irradiated allogeneic stimulator cells. It is suggested the different characteristics for the induction of either a primary or secondary cytotoxic T cell response reflect qualitative differences between unprimed T cells and memory T lymphocytes.

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

Enhanced in vitro immunogenicity of H-2 antigens in the presence of la antigens.

In a primary and secondary MLC the in vitro immunogenicity of allogeneic PHA induced blast cells (which lack i region coded determinants) was compared to that of LPS imduced blast cells. Unlike LPS induced blast lymphocytes (stimulator cells) which induced high cytotoxic activity, PHA induced blast cells were found to be poor stimulator cells in a primary MLC. Yet in a secondary MLC both types of stimulator cells induced cytotoxic activity equally well. Using one type of responder cells the relative immunogenicity of various stimulator cells incompatible on either the H-2K and H-2D region or on the i region, or on the complete H-2 complex, was compared. The magnitude of cytotoxic response induced in a strain combination differing at the complete H-2 complex exceeded by far the sum of separate responses obtained against the H-2D region, H-2K region and the i region coded determinants respectively. These results suggest that the presence of i region coded determinants on allogeneic stimulator cells enhance the in vitro immunogenicity of H-2K and H-2D region coded transplanatation antigens.

Animals↗
PubMed1976

Secondary cytotoxic allograft responses in vitro. III. The immunogenicity of allogeneic membrane fragments.

The immunogenicity of murine membrane fragments was tested both in primary and in secondary in vitro cytotoxic allograft responses, and compared to that of intact allogeneic stimulator cells. Allogeneic membrane fragments induced poor proliferative and cytotoxic responses in normal splenic responder cells. However reexposure of immune responder T cells to allogeneic membrane fragments triggered the generation of highly reactive cytotoxic T lymphocytes (CTL). Moreover, the generation of secondary CTL as induced by allogeneic membrane fragments was preceded by only a marginal cell proliferation. The results obtained are compatible with the concept that serologically defined (SD) antigens alone are capable of triggering alloimmune T cells to differentiate highly reactive secondary CTL.

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↗
PubMed1976

Cell-mediated immunity in lumphocytic choriomeningitis. I. The specificity of the cytotoxic T lymphocytes.

The specificity of cytotoxic T lymphocytes (CTL) generated during murine lymphocytic choriomeningitis (LCM) has been investigated. CTL were obtained from the spleens of mice injected i.p. with LCM virus. The cytotoxic activity of the CTL was tested in an in vitro 51Cr cytotoxicity assay using infected macrophages or fibroblasts as target cells. At the peak of the cytotoxic T cell response (7-8 days after infection) the cytotoxic action was restricted to syngeneic virus-infected target cells. Using H-2 recombinant mice the target antigen of the CTL generated could be identified as products coded for by either the H-2 K or H-2 D region of the major histocompatibility complex. I region identity between CTL and infected target cells was insufficient for optimal lysis to occur. During the early phase of LCM virus infection there was a transient phase during which non-infected H-2 histocompatible targets were lysed as efficiently as virus-infected target cells. This finding may suggest, that during the early phase of LCM disease self-reactive cytotoxic T lymphocytes are temporarily present in LCM virus-infected mice.

Animals↗
PubMed1975

Induction of cytotoxic T lymphocytes against I-region-coded determinants: in vitro evidence for a third histocompatibility locus in the mouse.

Determinants controlled by the I region of the murine H-2 complex provoked the generation of cytotoxic T lymphocytes (CTL) in both a secondary and primary mixed lymphocyte culture. The stimulating determinants appeared to be controlled by loci within the I-A subregion. The target antigens of the CTL generated were present on both lipopolysaccharide- and concanavalin-induced blast lymphocytes, but were barely detectable on phytohemagglutinin-induced blast cells. The stimulating capacity for CTL induction of a complete H-2 complex incompatibility by far exceeded the sum of H-2D/K-region and I-region incompatibility, respectively.

Animals↗
PubMed1975

T cell proliferation in the mixed lymphocyte culture does not necessarily result in the generation of cytotoxic T effector cells.

It was tested whether T lymphocytes, when stimulated in vitro by M locus-coded lymphocyte activating determinants (LAD), are able to mediate cytotoxic effector functions. The assay for cytotoxicity included both the use of purified appropriate target cells (i.e. purified lipopolysaccharide blasts) as well as the use of phytohemagglutinin dependent cytolysis as a model for detecting cytotoxic T lymphocytes (CTL). Although strong proliferative responses were obtained in the mixed lymphocyte culture, the T cell blast generated did not display any detectable cytotoxic effector function. Thus, it is concluded that LAD, at least in the M locus-dependent system, do have the capacity to induce T cell proliferation but do not induce CTL.

Animals↗