Biomedical subjects
Publications and source records attributed to C Carnaud.
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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.
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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.
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.
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.
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.
We have previously shown that the number of autologous rosette-forming cells (A-RFC) found in adult thymectomized mice (A-Tx) spleens was 15 times higher than that found in spleens of intact controls. We have therefore investigated both the specificity of A-RFC and their relationship with autoreactivity. Immunoadsorption experiments showed that while the incubation on allogeneic monolayers did not bring any modification in A-RFC levels. This result suggests that the formation of autologous rosettes is the manifestation of a true recognition event associated with the H-2 complex. A-Tx mice spleen cells injected into syngeneic recipients induced an enlargement of the afferent popliteal lymph node (LN). Ficoll-Triosil A-RFC depleted A-Tx spleen cells lost their capacity to induce this popliteal proliferation. Conversely, A-RFC recovered spleen cell suspensions obtained from the pellet of the Ficoll Triosil gradient kept their capacity of inducing auto-reactivity. Thus, it seems that A-RFC and lymphocytes stimulating the afferent LN belong to the same sub-population.