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Biomedical subjects

Z Lapidot

Publications and source records attributed to Z Lapidot.

4 recordsLinked to original sources

T lymphocytes of rheumatoid arthritis patients show augmented reactivity to a fraction of mycobacteria cross-reactive with cartilage.

An acetone-precipitable fraction of Mycobacterium tuberculosis cross-reacts with human cartilage. Immune responses to this antigen were assessed in 34 patients with rheumatoid arthritis, 16 patients with degenerative joint disease, and 15 healthy controls. The RA patients differed from the other two groups in having more pronounced T lymphocyte responses to the antigen; their serum antibody levels were not higher. The responses of RA patients varied with duration of disease. In the first year (7 patients) T lymphocyte reactivity was increased in the synovial exudates of affected joints but not in peripheral blood, whereas the 19 with disease of 1-10 years' duration showed high reactivity in peripheral blood; in the 8 with disease for more than 10 years, lymphocyte reactivity did not differ from that in the patients with degenerative joint disease or the healthy controls. The observation that the three groups did not differ in their responses to streptococci and a T-cell mitogen indicates that reactivity of the RA patients to the mycobacterial fraction was specific. These results raise the possibility that bacterial antigens cross-reactive with cartilage proteoglycans may be relevant to the pathogenesis of RA.

Adult

Does stem cell self renewal and progenitor cell commitment operate through an effector-memory cell mechanism?

We propose a model for stem cell self renewal and transition into commitment towards a variety of cell lineages. In this model the production of both "effector cells" (as represented by the mature cells in the different cell lineages) and of progenitor "memory" lymphocytes, takes place concomitantly. The experimental evidence supporting this model is as follows: Pure lymphocytic suspensions (PLS) are established and persist in culture when nude mouse-spleen and lymph-node cells are maintained on X-irradiated fibroblast monolayers in the presence of the S-phase cytotoxic agent cytosine arabinoside (Ara-C). From these PLS the following colony types can be initiated by the corresponding inducing (stimulating) factors (CSF): histiocytes (tissue macrophages) - CSF-1; granulocytes-macrophages (GM) - CSF-GM; mast cells - MMSF; granular-NK mucus secreting cells - IL-2; and multilineage colonies - IL-3. Mitotically active blast cells (formed by transformation of lymphocytes), condense into motile small cells when the stimulatory factor is removed. These "memory" lymphocytes are committed as they carry the receptors for the specific CSF; they respond by retransformation into blast cells. A dramatic increase in mast-cell colony forming cells is found in bone marrow, spleen and lymph-nodes of mice infected with Schistosoma mansoni. By maintaining PLS with both Ara-C and each of the CSFs and then titrating the incidence of CFC in the residual PLS, we find that each one of the CSFs acts on an independent set of cells in the PLS to produce the corresponding colony type. Finally, the concept suggests that the various blast cells carrying the receptors, undergo condensation into memory lymphocytes when dissociated from the environment prevailed by the corresponding CSF. In this way pluripotential blast-cells condense into motile lymphocytes which are committed to pluripotentiality.

Animals

Granular natural-killer cells develop into mucus-secreting cells.

Colonies of granular natural-killer cells selectively develop in lymph-node cell cultures of nude mice after stimulation with rat T-cell growth factor. When these cells are grown on X-irradiated monolayers prepared from 16-18-day-old mouse embryos, they are triggered to synthesize and secrete a sulphated glycoprotein that can be identified as mucus. As a result of an erosive process of the granules, the mucoid material accumulates in pools in the cytoplasm matrix. The secretion is operated through a process of budding of double-membrane-bound vesicles. The successful triggering of mucous synthesis is interpreted by the successful growth of those mesenchymal cells in the embryonic monolayer that function in the induction of epithelial morphogenesis in the developing embryo.

Animals

Interleukin-1 secretion by blood monocytes of septic premature infants.

This study examined lipopolysaccharide (LPS) induced in vitro secretion of interleukin-1 (IL-1) by peripheral blood monocytes from pre-term infants with and without sepsis. Thirteen pre-term babies were tested; eight were completely healthy and five suffered from six episodes of sepsis. The latter group was tested both in the acute septic phase and in the convalescent period. IL-1 secretion by monocytes derived from septic pre-term infants was lower, but not significantly different from healthy pre-term infants (7.1 +/- 1.0 U/ml versus 8.1 +/- 0.9 U/ml, respectively). IL-1 secretion by monocytes of eight control full-term babies was in the same range (8.4 +/- 0.6 U/ml). In the convalescent period IL-1 secretion by monocytes from septic pre-term babies increased (9.0 +/- 0.3 U/ml) and was significantly higher than values measured during acute infection (p less than 0.05). Septic premature babies were also found to have higher absolute blood neutrophil concentration (p less than 0.001), but their body temperature did not increase along the infectious stage. The decreased secretion of IL-1 by monocytes from pre-term babies in the acute phase of infection compared to the convalescent period may have contributed to their inability to mount appropriate immunological as well as inflammatory responses. Sepsis promoting IL-1 production in vivo may have limited the monocytes' capacity for LPS stimulated IL-1 synthesis in vitro.

Acute Disease