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Biomedical subjects

P Liacopoulos

Publications and source records attributed to P Liacopoulos.

At least 19 recordsLinked to original sources

The macrophage, target cell of the synthetic adjuvant muramyl dipeptide.

The mechanism of adjuvant activity of the synthetic glycopeptide N-acetylmuramul-L-alanyl-D-isoglutamine or muramyl dipeptide (MDP) was studied using in vitro plaque-forming cell (PFC) response to sheep erythrocytes (SRBC). Addition of MDP to DBA/2 mouse spleen cell cultures resulted regularly in a 2 to 3-fold increase of PFC numbers/10(6) recovered cells (p less than 0.01). Supernates (SPN) from MDP-stimulated cultures added to standard spleen cell + SRBC cultures brought about even more important increases of PFC numbers (p less than 0.01 to p less than 0.001). SPN from cultures supplemented with MDP alone (without SRBC) were more active than those of cell + MDP + SRBC cultures, and SPN removed on day 3 of culture were more active than those of day 5. This activity of SPN was maintained accross an H-2 histocompatibility barrier. Although pretreatment of spleen cells with anti-theta antigen serum entirely suppressed the anti-SRBC PFC response in spite of the presence of MDP, SPN from these cultures were as active as SPN from normal spleen cell MDP-stimulated cultures. In contrast, pretreatment of spleen cells with specific rabbit anti-mouse macrophage serum entirely suppressed both anti-SRBC response and SPN activity. It was concluded that the target cell for MDP is the macrophage which releases factors ultimately acting on B cells through T cell mediation.

Acetylmuramyl-Alanyl-Isoglutamine

The capacity of histocompatibility antigens solubilized in hypertonic salt solution to induce allograft tolerance in rats.

Treatment of Fisher rats (AgB 1,26,28) with a soluble extract of histocompatibility antigens (SAE) prepared from the liver of donor August rats (AgB 5, 28, 31) associated with a few injections of anti-lymphocyte serum (ALS) provoked a specific prolongation of the median survival time of skin grafts from 27.6 +/- 11.4 days in ALS-treated controls to 55.1 +/- 8.8 days (p less than 0.01). The SAE was obtained from liver homogenates by hypertonic KCl (3M) extraction. Further purification by chromatography in DEAE-cellulose column resulted in the separation of fractions possessing a specific inhibitory activity on a Fisher anti-August cytotoxic serum that was almost 100 times higher than that of the initial SAE preparation. Analysis of the state of unresponsiveness induced by SAE and ALS showed that most of the unresponsive animals had in their serum blocking factors. On the other hand, in vitro study of proliferative and cytotoxic components of cell-mediated immunity by mixed lymphocyte reaction and cell-mediated lympholysis, respectively, showed that the proliferative reactivity remained unimpaired whereas the cytotoxic reactivity was clearly inhibited in the tested animals. These results suggest that a central tolerance to histocompatibility antigens (equivalent to those coded by the K and D end in the mouse) could have been induced in the experimental animals whereas reactivity to Ia region antigens was not affected.

Animals

Human lymphoid cells of the intestinal mucosa showing specificity for both immunoglobulin light and heavy chains.

The presence of single human lymphoid cells expressing on the one hand both kappa and lambda light chain and on the other hand either both mu and alpha or both mu and gamma heavy chains, was observed in the intestinal mucosa. The variability of the frequency of such cells, both from one subject to another, or in the same sample, is a characteristic of this population.

Humans

[Cells secreting antibodies originate from cells secreting immunoglobulins without a detectable antibody function for the antigen injected].

Cells secreting immunoglobulins without detectable antibody function arising after an injection of horseradish peroxidase were micromanipulated from the center of haemolytic plaques of Sheep red blood cells coated with anti-Ig antibodies. These cells were cultured individually for 48 hrs, with irradiated cells as feeder layer and in the presence of the immunogen and of LPS. It was shown that after this time 22% of the immunoglobulin-secreting cells had generated antiperoxidase antibody-secreting cells or were transformed into antibody-secreting cells.

Animals

[Lymphoid cells of the intestinal mucosa with double kappa and lambda specificity in normal man].

The presence of lymphoid cells possessing both kappa and lambda specificities has been observed in the intestinal mucosa of normal subjects. The variability in the number of such cells in different sections of the same sample and in different subjects seems to be a characteristic of this cell population and may reflect the high activity of the immune system in the small intestine.

Fluorescent Antibody Technique

Inhibition of mixed lymphocyte reactions in humans after immunization with tetanus toxoid.

Immunization of humans with tetanus toxoid (TT) results in an inhibition of the reactivity of peripheral lymphocytes to TT as well as to one-way mixed lymphocyte reaction. The strongest inhibition was observed in cells taken 3 or 7 days after immunization. These reactivities reappeared on the 14th day and reached their initial levels by the 21st day after immunization. The role of the various cell types was studied by culturing separately purified T or B lymphocytes taken on day 7 after immunization. B cells alone are not stimulated by TT or allogeneic cells. Purified T cells are stimulated much more than the initial total cell population. When B cells were mixed and cultured along with T cells, a suppressor effect upon stimulation appeared which reduced 3H-thymidine incorporation to the levels of the initial population. Treatment with 5-bromodeoxyuridine followed by exposure to light of cells stimulated with TT abrogated their ability to respond to subsequent stimulation with TT; whereas the responsiveness of treated cells to allogeneic lymphocytes was not significantly affected and vice versa. These results suggest that each stimulator activated a separate population of T cells but that in vivo immunization provoked the development of both a specific and nonspecific suppressor activity. Most probably this suppressor activity was brought about by adherent, surface Ig-bearing (B) cells.

Adult

Lymphoid cells of the normal man intestinal mucosa possessing both kappa and lambda light chain specifities.

The presence of lymphoid cells possessing both kappa and lambda specificities has been observed in the intestinal mucosa of normal subjects. The variability in the number of such cells in different sections of the same sample and in different subjects seems to be a characteristic of this cell population and may reflect the high activity of the immune system in the gut.

Antibody-Producing Cells

Unrelated delayed hypersensitivity reactions accelerate the recovery of immunological responsiveness of specifically depleted cell populations.

Normal CBA mouse spleen cells were specifically depleted of cells spontaneously reacting to pigeon erythrocytes (PRBC) by two methods, the first allows specific depletion of anti-PRBC thymus derived (T) rosette forming cells (RFC) whereas the second depletes bone marrow derived (B) anti-PRBC hemolytic plaque forming cells (PFC). Depleted populations transferred into lethally irradiated syngeneic recipients and stimulated with PRBC failed to develop any significant response but they normally responded to a stimulation with sheep erythrocytes (SRBC). When spleen cells were taken from mice skin painted with picryl (trinitrophenyl: TNP) chloride 12 days before and the recipients were challenged in the same way and stimulated with PRBC, they become capable of producing a definite response to this antigen. Moreover in these animals, a consistent although low number of cells was found, which simultaneously reacted to both native PRBC and TNP conjugated SRBC. These findings show that unrelated delayed hypersensitivity reactions promote the immunological recovery of specifically depleted cell populations.

Animals