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M Röllinghoff

Publications and source records attributed to M Röllinghoff.

At least 163 records · Page 9Linked to original sources
PubMed1982

T-T cell interactions during cytotoxic T cell responses. IV. Murine lymphoid dendritic cells are powerful stimulators for helper T lymphocytes.

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-positive cells resulted in the production of interleukin 2. The data are discussed in view of the recently formulated interleukin model as a minimal scheme to explain T-T cell interactions during the in vitro induction of cytotoxic T lymphocytes.

Animals↗
PubMed1982

The in vivo effects of interleukin 2 (TCGF).

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 in the generation of highly reactive T-helper cells, as well as in the generation of alloreactive CTL.

Animals↗
PubMed1982

Interleukin 2 induction in Lyt 1+ 23- T cells from Listeria monocytogenes-immune mice.

Peritoneal exudate T lymphocytes from mice experimentally infected with the intracellular bacterium Listeria monocytogenes secreted high interleukin 2 activities after interaction with syngeneic normal macrophage presenting listerial antigen in vitro. L. monocytogenes-immune cells secreting IL 2 were radioresistant and bore the phenotype Thy 1(+) Lyt 1(+)23(-).

Animals↗
PubMed1982

Interactions of human T cell subsets during the induction of cytotoxic T lymphocytes: the role of interleukins.

In this work we study the role of subsets of human T cells, detectable by the OKT series of monoclonal antibodies, in the production of and the response to the lymphokine interleukin-2 (Il-2) during the course of an allogeneic cytotoxic T lymphocyte response in vitro. The results obtained establish that the Il-2 producer cells reside within the OKT4 positive T cell subset. Once produced, Il-2 mediates the clonal expansion of alloantigen-activated cytotoxic T killer cells which reside in the OKT8 positive T cell subset. Il-2 appears to have no mitogenic activity on the activated OKT4 positive T cells which produce the lymphokine. In order to release Il-2, the OKT4 positive T cell requires a stimulus, such as allogeneic cells or the lectin phytohaemagglutinin A (PHA). Macrophages are also required for Il-2 production, but the macrophage requirement can be bypassed by a soluble macrophage product as found in supernatants of lymphocyte cultures stimulated with lipopolysaccharide (LPS), the biological activity presumably representing Interleukin-1 (Il-1).

Antibodies, Monoclonal↗
PubMed1981

Lyt-23+ cyclophosphamide-sensitive T cells regulate the activity of an interleukin 2 inhibitor in vivo.

Sera of thymus-bearing normal mice contain high levels of Interleukin 2 (II-2) inhibitor, whereas sera of athymic nu/nu mice do not. Evidence is presented that cyclophosphamide-sensitive Lyt-23+ T cells induce high II-2 inhibitor activity in the recipient nu/nu mice in the course of a graft-vs.-host reaction. The II-2 inhibitor has an approximately 50,000 mol wt. Its function is neither antigen specific nor H-2 restricted. During ontogeny, its activity parallels the development of T cell reactivity, i.e., it is absent both in the amniotic fluid and in sera of unborn mice, but increases to high levels during the early postnatal phase. The II-2 inhibitor described is viewed as an example of a T cell-dependent, in vivo regulatory mechanism able to effectively counteract the nonspecific activity of the Lyt-1+ helper T cell-derived II-2. Because the II-2 inhibitor activity is rather high in vivo, II-2 activity will exist only in close proximity to its producer cell, thereby maintaining specificity during the in vivo induction of cytotoxic T lymphocytes

Animals↗
PubMed1981

Frequency analysis of cytotoxic T lymphocyte precursors in chimeric mice. Evidence for intrathymic maturation of clonally distinct self-major histocompatibility complex- and allo-major histocompatiblilty complex-restricted virus-specific T cells.

To study whether the thymic major histocompatibility complex (MHC) imposes a constraint on the receptor repertoire of maturating cytotoxic T lymphocyte (CTL) precursors, the restriction phenotypes of virus-specific CTL of MHC-compatible and of MHC-incompatible thymus- and bone marrow-grafted (A X B)F1 chimeric mice were compared. Dependent on the mode of in vitro sensitization, thymocytes or splenocytes of both types of chimeric mice generated Sendai virus-specific, self-MHC-or allo-MHC-restricted CTL. By applying the limiting-dilution technique, the CTL-precursor (CTL-P) frequencies of self-MHC-restricted and allo-MHC-restricted virus-specific T cells as well as of alloreactive T cells were determined. The data obtained revealed that independent of MHC differences between thymus and bone marrow, the frequencies of self-MHC-restricted and allo-MHC-restricted CTL-P were comparable, and in the same older of magnitude as those previously determined in conventionally reared mice. Self-MHC-restricted, virus-specific CTL-P were in a three- to fivefold excess over allo-MHC-restricted CTL-P. A segregation analysis revealed that clonally distinct CTL-P give rise to either self-restricted or allo-MHC-restricted, virus-specific CTL. Both sets were found not only in the spleen, but also in the thymus of chimeric mice, formally demonstrating the intrathymic differentiation pathway of self-MHC as well of allo-MHC-restricted CTL-P. These data reveal no major constraint of the thymic MHC on the capacity of T cells to recognize viral antigens either in the context of self-MHC or of allogeneic MHC products.

Animals↗
PubMed1981

H-2 restriction as a consequence of intentional priming. Frequency analysis of alloantigen-restricted, trinitrophenyl-specific cytotoxic T lymphocyte precursors within thymocytes of normal mice.

An in vitro acute-depletion protocol was used to detect trinitrophenyl (TNP)-specific, allo-major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes (CTL) within thymocytes of inbred mice. After removal of alloreactivity, the negatively selected cells could be sensitized to become TNP-specific, allo-MHC-restricted cytotoxic T cells. A precursors frequency analysis revealed a three- to ninefold lower frequency of allo-MHC-restricted CTL precursors (CTL-P) as compared to self-MHC-restricted CTL-P. The specificity analysis of clonally distributed allo-MHC-restricted CTL-P excluded cross-reactivity as an explanation of allo-MHC restriction. These results provide direct evidence that thymic T cells are composed of a mixture of self-MHC- and allo-MHC-restricted immunocompetent T cells and that antigen-driven selection of precommitted T cells dictates the H-2-restriction phenotype, i.e., H-2 restriction is a consequence of priming.

Animals↗
PubMed1981

Cyclosporin A mediates immunosuppression of primary cytotoxic T cell responses by impairing the release of interleukin 1 and interleukin 2.

The site of action of the immunosuppressive drug cyclosporin A in in vitro cytotoxic allograft responses has been localized. General cytotoxic effects of the drug on proliferating T cells became apparent at concentrations of 500-1000 ng/ml, while selective effects were observed at concentrations of 10-100 ng/ml. The selective effects included a blockade of interleukin 2 release from activated T helper cells on the one hand and inhibition of interleukin 1 release from splenic adherent cells on the other. While cyclosporin A did not interfere with the intracellular events required for the activation and subsequent clonal expansion of alloreactive T cells, the lack of interleukin 1 and interleukin 2 induced by cyclosporin A results in an inability of T responder cells to mount cytotoxic allograft responses in vitro.

Animals↗
PubMed1980

Alloreactive and H-2-restricted Lyt 23 cytotoxic T lymphocytes derive from a common pool of antecedent Lyt 123 precursors.

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.

Animals↗
PubMed1980

T cell-mediated cytotoxic immune responsiveness of chimeric mice bearing a thymus graft fully allogeneic to the graft of lymphoid stem cells.

Fully allogeneic, chimeric mice were established by adult thymectomy of (A x B) F1 animals, grafting parental A-type thymus under the kidney capsula, followed by lethal (900 rd) irradiation and reconstitution with B parental-type bone marrow cells treated with xenogeneic anti-T cell antiserum plus complement. Following in vivo sensitization with inactivated Sendai virus (SV) suspensions, no virus-specific T cells could be detected within the spleen cells of the mice. Upon stimulation with third-party allogenic cells in a primary mixed lymphocyte culture, spleen cells of all animals generated alloreactive cytotoxic T lymphocytes (CLT). More interestingly, upon secondary in vitro stimulation with inactivated SV-conjugated B-type stimulator cells, B-type-restricted, virus-specific CTL were inducible in each case. Upon restimulation with SV-conjugated A-type stimulator cells, A being the H-2 type of the grafted thymus, T cells of some but no all mice generated A-type-restricted, virus-specific CTL. The data suggest that in allogeneic, chimeric mice virus-specific CTL can be induced. Moreover, virus-specific CTL, restricted to the H-2 type of the lymphoid stem cell inoculum, are more readily inducible than those restricted to the H-2 type of the allogeneic thymus.

Animals↗
PubMed1980

T-T cell interactions during in vitro cytotoxic T lymphocyte responses. III. Antigen-specific T helper cells release nonspecific mediator(s) able to help induction of H-2-restricted cytotoxic T lymphocyte responses across cell-impermeable membranes.

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 nonrestricted manner. The data suggest that similar rules govern T-T cell interactions in alloreactive and H-2-restricted CTL responses.

Animals↗
PubMed1980

T cell mediated cytotoxic immune reactivity of bone marrow reconstituted chimeric mice.

The capacity of bone marrow reconstituted chimeric mice to mount sendai virus specific H-2 restricted as well as alloreactive cytotoxic T-cell responses has been investigated. Chimeras of the type a leads to (a x b)F1 and (a x b)F1 leads to a were used. In addition chimeras produced with (a x b)F1 mice grafted under the kidney capsula with a type parental thymus, thymectomised, lethally irradiated and reconstituted with either a, (a x b)F1 or b type bone marrow cells were tested. In agreement with the data of Zinkernagel and Bevan it was noted that virus specific T cells of semi-allogeneic chimeric mice are able to recognise virus antigens in the context of the MHC of the thymus in which they have maturated. The unexpected finding was that fully allogeneic chimeras were able to mount both alloreactive CTL and H-2 restricted, virus specific CTL. The H-2 restricted CTL detected were preferentially restricted to their own MHC type. In some animals also virus specific CTL restricted to the allogeneic thymus MHC type were observed. Data are also presented to indicate that longterm cultured bone marrow cells have the potential to repopulate lethally irradiated mice.

Animals↗
PubMed1980

Herpes-Simplex-virus-specific, H-2Dk-restricted T lymphocytes bear receptors for H-2Dd alloantigen.

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 that the phenomenon of H-2-restricted versus nonrestricted T-cell reactivity is not due to distinct T-cell subsets, but rather is dependent on the antigeneic determinants recognized.

Animals↗