Franco Quagliata

Prostaglandin E1 as a regulator of lymphocyte function: Selective action on B lymphocytes and synergy with procarbazine in depression of immune responses☆

The possibility that prostaglandin (PG) E1 can regulate lymphocyte function in vivo was studied. In conjunction with procarbazine hydrochloride, a powerful immunosuppressive agent whose main target is the thymus and thymus-derived (T) cells, PGE1 had a synergistic effect in prolonging homograft survival, though alone it had no effect on this immune response. The main lymphocyte target of PGE1 appeared to be bone marrow-derived (B) as determined from direct assessment of total, complement receptor and θ-positive lymphocytes in the spleen and by histological evaluation.

Competence of thoracic duct cells in the transfer of adjuvant disease and delayed hypersensitivity. Evidence that mycobacterial components are required for the successful transfer of the disease

Abstract Transfer of rat adjuvant disease into syngeneic recipients was achieved with lymph node and spleen cells from adjuvant injected donors, but not with washed thoracic duct (TD) cells, despite the fact that these were capable of transferring delayed hypersensitivity (DH) to PPD. Addition of mycobacteria enabled the TD cells to transfer disease. Injection of adjuvant caused accelerated development of disease in the recipients of sensitized TD cells. Since addition of mycobacterial components, probably already present in lymph node and spleen cell preparations, was necessary to transfer disease with sensitized TD cells, it appears unnecessary to invoke an autoimmune or viral etiology for the disease. It is concluded that adjuvant disease results from prolonged DH type reactions to mycobacterial components deposited in the sites of inflammation. TD cells drained late were more efficient than those drained early after cannulation in the transfer of DH to PPD. This was probably due to changes in the proportions of different cell populations present in the TD lymph.

The anomalous capping behavior of chronic lymphocytic leukemia lymphocytes: studies with an antilymphocyte antiserum.

Abstract After exposure to antiimmunoglobulin antiserum or concanavalin A, lymphocytes from patients with chronic lymphocytic leukemia (CLL) have shown fewer caps than those from normal subjects. Since this anomalous behavior might stem from a decrease in the amount of ligand bound to lymphocytes from patients with this disorder, experimental conditions were devised to provide a ligand which could be expected to react with these lymphocytes. An antiserum to CLL lymphocytes which cross-reacted with normal lymphocytes was raised in rabbits. Cap formation by this antiserum was significantly lower with CLL than with normal blood or tonsil lymphocytes. Following exposure to the immunoglobulin fraction of this antiserum, only 10.8% of CLL lymphocytes displayed caps as opposed to 51.3 and 46.6%, respectively, of normal blood or tonsil lymphocytes. Radioiodinated antibody was used to quantitate the antilymphocyte immunoglobulin bound. Despite the defective capping of CLL lymphocytes, equivalent amounts of antilymphocytic immunoglobulin (up to a maximum of 2.1 × 10 6 molecules/cell) were bound to normal, tonsil, or CLL lymphocytes. These findings were unaltered by the removal of T cells. These data indicate that the abnormal capping of CLL lymphocytes is not caused by a decreased amount of ligand bound to the membrane receptors.

Immunosuppression by procarbazine: I. Sites of action of the drug and effect on adjuvant arthritis and circulating antibody responses

Abstract The effect of procarbazine hydrochloride on adjuvant arthritis and on circulating antibody responses in the rat was studied. Procarbazine had a profoundly depressing effect on both adjuvant arthritis and the circulating antibody response to ovalbumin (OA). In contrast, it had no effect on the immune response to sheep erythrocytes (SRBC) alone; the presence of adjuvant, however, enhanced the response to SRBC, and this enhancement was suppressed by procarbazine. Preinjection with adjuvant enhanced the response to OA given at a different site: procarbazine treatment at the time of adjuvant injection suppressed this enhancement. These results taken in conjunction with histological observations, reinforce the idea that the initial effect of the drug is predominantly on the thymus and thymus-dependent cell populations, though prolonged treatment may also affect the bone marrow. They also give a clue to the mode of action of adjuvant in enhancing immune responsiveness. It is suggested that judicious use of procarbazine may assist fine dissection of various components of the immune response.

Cellular events in tolerance. II. Thymus-bone marrow cell cooperation in the immune response to BSA in Wistar Furth rats.

Abstract Normal bone marrow cells from Wistar Furth rats were competent to transfer immune responsiveness to bovine serum albumin to thymectomised, irradiated, syngeneic recipients. When the bone marrow cells were taken from donors thymectomised early in life they were incompetent, but competence was restored by addition of normal thymus cells. It was concluded that normal Wistar Furth bone marrow cells contain some thymus-derived cells. Thymus cells from tolerant donors were less effective in cooperation with bone marrow cells, however the thymus cells appeared less tolerant than their donors.

Mechanism of Interaction between Immune Complexes and Receptors for Antibody on Macrophages

Follicular localization of antigen depends on the presence of antibody (1–3). It has been suggested (1) that one of the cells involved in trapping of antigen-antibody complexes is the dendritic macrophage. This cell is similar to the circulating monocyte and macrophage, and it is possible that, like them, it possesses separate surface receptors for antibody and for modified complement (4–6), Either or both of these receptors may be necessary for antigen localization.

Effetto immunosoppressivo di prodotti batterici extracellulari.Effetto sulla malattia da adiuvante

RiassuntoNel ratto, la risposta infiammatoria locale all’iniezione di adiuvante e la successiva comparsa della malattia da adiuvante sono state notevolmente soppresse mediante somministrazione di prodotti extracellulati di alcune specie batteriche. Ptodotti dellaS. typhimurium hanno causato profonda leucopenia, inibizione della risposta anticorpale circolante e soppressione della malattia da adiuvante. Prodotti delloStrep. pyogenes non hanno causato leucopenia né inibizione della produzione di anticorpi circolanti, inducendo tuttavia una marcata inibizione della malattia da adiuvante. Prodotti delloStrep. pneumoniae hanno mostrato un effetto simile ma meno marcato, mentre prodotti delloStaph. aureus sono risultati del tutto inefficaci.SummaryBoth the inflammatory response at the site of adjuvant injection and the subsequent development of adjuvant disease in the rat were markedly suppressed by the administration of extracellular products from some bacterial species.S. typhimurium products caused marked leucopenia, inhibition of circulating antibody response, and suppression of adjuvant disease.Strep, pyogenes products did not cause leucopenia or inhibition of circulating antibody response, yet caused marked inhibition of adjuvant disease.Strep. pneumoniae products had similar, but less marked effects, whileStaph. aureus products were completely ineffective.Nel ratto, la risposta infiammatoria locale all’iniezione di adiuvante e la successiva comparsa della malattia da adiuvante sono state notevolmente soppresse mediante somministrazione di prodotti extracellulati di alcune specie batteriche. Ptodotti dellaS. typhimurium hanno causato profonda leucopenia, inibizione della risposta anticorpale circolante e soppressione della malattia da adiuvante. Prodotti delloStrep. pyogenes non hanno causato leucopenia ne inibizione della produzione di anticorpi circolanti, inducendo tuttavia una marcata inibizione della malattia da adiuvante. Prodotti delloStrep. pneumoniae hanno mostrato un effetto simile ma meno marcato, mentre prodotti delloStaph. aureus sono risultati del tutto inefficaci.