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C Carnaud

Publications and source records attributed to C Carnaud.

At least 73 records · Page 4Linked to original sources

Mechanisms of cell-mediated cytotoxicity in mice rejecting xenogeneic human lymphoblastoid cells.

The in vivo immunization of mice with human lymphoblastoid cell line LNH13 generates direct cell-mediated cytotoxicity by spleen cells. The lytic activity appears as early as day 3 after the intraperitoneal inoculation of 7.5 x 10(6) cells and persists at least until day 11. The killer cells do not adhere to plastic and are not retained on nylon wool columns or on Degalan beads coated with mouse Ig plus rabbit-anti-mouse Ig. The effector cells are partly inhibited by treatment with anti-Thy-1.2 serum plus complement, but this inhibition appears to be non-specific since anti-serum alone or normal serum plus complement have the same effects. Heat-aggregated IgG strongly inhibits cytotoxicity, indicating that the effector cells are Fc-positive and that such receptors are implicated in lysis. Altogether, these features strongly argue for an ADCC phenomenon. The involvement of antibodies is demonstrated by the fact that eluates (56 degrees C, 30 min) from immune cells alone induce lysis in the presence of normal spleen cells as effectors. The lytic activity of these eluates can be removed by specific adsorption on protein A coupled to Sepharose beads and on the human lymphoid target cells. Positive complementation between immune and non-immune spleen cells suggest that the arming process may occur in vitro during the assay, when antibodies are released by plasmacytes.

Animals↗

Selective depression of the xenogeneic cell-mediated lympholysis in systemic lupus erythematosus.

The immunological responsiveness of a panel of 17 patients with systemic lupus erythematosus (SLE) was studied in an in vitro model of xenogeneic sensitization against mouse lymphoid cells. Generation of cytotoxic thymus-derived (T) cells evaluated by a chromium release assay against labeled target cells was found to be drastically impaired in these lupus patients. Such depression was independent of drug therapy at the time of the study, clinical status, and other immunological parameters such as antibodies against native DNA, complement levels, cryoglobulinemia, circulating immune complexes, or T- and bone marrow-derived (B)-cell numbers. In contrast to the cytotoxic response, the proliferative responses to phytohemagglutinin, to allogeneic lymphocytes, and to xenogeneic lymphocytes were not significantly different from those of normal individuals. The latter response was shown to be H-2 restricted with the primed lymphocyte test. These results suggest the presence of a selective defect in the generation or in the expression of killer cells rather than a deficiency in antigen recognition by T cells. The role of serum factor(s) was examined by educating the lymphocytes of normal subjects in the presence of serum from SLE patients. Such manipulation affected both the generation of killer cells and the proliferative response. Finally our observations indicate that depression of cell-mediated immunity in SLE patients may be associated with several mechanisms including a cellular one, specifically affecting the generation of killer T cells, and a humoral one possibly as a result of antilymphocytic antibodies and(or) immune complexes.

Adult↗

Increased stimulatory capacity of spleen cells from adult thymectomized mice in mixed lymphocyte reactions.

Conflicting results have been reported concerning the effect of adult thymectomy (A-Tx) on the mixed lymphocyte reaction (MLR) response. Our purpose was to test the reverse question, namely the effect of A-Tx on the stimulatory capacity of mouse lymphocytes carrying allelic disparities at the Mls and the H-2 loci. Spleen cells from A-Tx CBA donors were found to be significantly more stimulating than cells from normal donors. That A-Tx could eliminate suppressor T cells involved in MLR regulation or in preventing back stimulation is not likely according to our data. An increment in expression or in accessibility of Mls or H-2 antigenic determinants induced by A-Tx is no more likely, since a smilar increase in lymphocyte proliferation was observed in syngeneic cultures. The most probable explanation remains that A-Tx discloses a strongly stimulatory subpopulation, perhaps acting in part nonspecifically. The hypothesis of an enrichment in B cells versus a loss of T cells is not compatible with our findings, since B-cell-enriched fractions from various origins never attained the stimulating ability disclosed by A-Tx cells. Moreover, the cell involved is theta-positive, although slightly nylon-wool-adherent, and thus shares several properties with immature T cells involved in auto-rosette formation.

Aging↗

Thymic factors.

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Animals↗

Spleen-cell reactivity against transplanted neurogenic rat tumors induced by ethylnitrosourea: uncovering of tumor specificity after removal of complement-receptor-bearing lymphocytes.

Spleen cells from BDIX-rats bearing either GVlAl-tumor (a syngeneic mixed glioma) or NVlAc-tumor (a cloned syngeneic neurinoma of the peripheral nervous system) were cytotoxic to both tumor cells in vitro. However, the tumors displayed individually distinct antigenic specificities by in vivo rejection tests. Their in vitro cross-reactivity disappeared when a particular subpopulation of the spleen cells was used. The procedure of lymphocyte purification included three consecutive steps: treatment with carbonyl iron and magnetism, passage through a nylon wool column, and finally removal of complement receptor-bearing cells present in the colum-excluded population. Cross-reactivity between the syngeneic tumors persisted after the first two steps of lymphocyte purification. In contrast, specific cytotoxic reactions were observed against each individual tumor subsequent to the removal of the remaining C3 receptor-positive but surface Ig-negative cells. While killer cells were present in normal spleen-cell populations, these were almost completely eliminated by passage through the nylon wool column.

Animals↗

In vitro "education" on autologous human sarcoma generates non-specific killer cells.

The cytotoxic effects mediated by lymphocytes from cancer patients after in vitro "education" on autologous tumor cells have been investigated. Peripheral blood lymphocytes from three sarcoma patients were cultivated on autologous tumor-cell monolayers and tested thereafter in a micro-cytotoxicity assay against tumor and fibroblast cells. This procedure led to the progeny of non-specific killer cells. As the phenomenon did not occur when the same lymphocytes were co-cultivated with autologous fibroblasts, the generation of non-specific effector cells may have been caused by specific antigenic triggering. The presence of autologous serum during "education" was found to inhibit the manifestation and/or the generation of killer cells. The same serum was without effect when added during the cytotoxicity assay only.

Antigen-Antibody Reactions↗

The role of thymus on autosensitization against syngeneic normal and malignant cells.

Mouse lymphocytes were exposed to syngeneic fibroblasts and tumor cells in Millipore chambers inserted into the peritoneal cavity of intact and thymectomized mice. Autosensitization to fibroblasts occurred only if the chambers were carried by thymectomized mice. Sensitization to tumor-specific antigens also took place in intact mice. If thymic extract was administered to thymectomized mice autosensitization in the chambers was inhibited.

Animals↗

Increased incidence of urethane induced lung adenomata by autosensitized lymphocytes.

The present work investigates the influence of autosensitized lymphocytes on the carcinogenic response of the host. Urethane treated SWR mice received 6 fortnightly injections of lymphocytes sensitized in vitro against syngeneic fibroblasts. An increased incidence of lung adenomata was found in these mice compared with controls injected with unsensitized lymphoid cells or with lymphoid cells sensitized against unrelated transplantation antigens. Autosensitized lymphocytes also modified the response of host lymphoid cells to concanavalin A or to stimulation in a mixed lymphocyte culture assay. These results indicate that autoimmune lymphocytes may increase susceptibility of a host to the induction of tumours.

Adenoma↗

Increased reactivity of mouse spleen cells sensitized in vitro against syngeneic tumor cells in the presence of a thymic humoral factor.

Unprimed mouse spleen cells cultured in vitro on syngeneic tumor cell monolayers have been previously shown to become specifically sensitized and to mediate cytotoxicity against the same type of tumor cells. This complete in vitro system of cell-mediated response has been presently used to test the effect of a thymic humoral factor (THF) upon the differentiation process leading to the generation of specifically committed lymphocytes. Culture media were supplemented with 2% THF during either the sensitization or effector phase, or both phases of the reaction. Whereas the addition of THF during both phases or during sensitization only resulted in a significant increase in the cytotoxicity index, THF added during the effector phase was ineffective. The behavior of unsensitized spleen cells and of spleen cells sensitized against nonrelated transplantation antigens remained unmodified by THF. After showing that the entire reaction is mediated by lymphocytes of thymic origin, THF was directly tested on T or B spleen cells. It was found that only T cells reacted to THF by an increased cytotoxic capacity, while B cells remained inactive after addition of THF. It was therefore concluded that THF activates a postthymic population of lymphoid cells, transforming them into fully competent lymphocytes.

Animals↗