Abraham Klajman

Clonal analysis of human tumor infiltrating lymphocytes reactive with autologous tumor cells: different target cell specificities of NK-like and cytotoxic T-cell clones.

Lymphocytes, derived from surgically resected lung carcinoid tissue, were stimulated in mixed culture with irradiated autologous tumor cells (MLTC). The autologous MLTC-stimulated lymphocytes were found to have killing activity against both autologous tumor cells and NK-sensitive target cells. The lymphoblasts generated during MLTC were isolated and cloned under limiting dilution conditions in the presence of interleukin 2. The cloned cell lines were analyzed for cell phenotype and tested for cytotoxic activity. Three cloned cell lines, out of 19 tested, were found to be cytotoxic either against NK-sensitive target cells (natural killers) or the autologous tumor cells. Two clones, having OKT8 phenotype, caused no lysis of the autologous tumor cells, though both exerted NK-like activity against K562 cells. Only one clone with OKT4 phenotype showed specific cytotoxic activity against the autologous tumor, but no NK-like activity against a panel of tumor target cells. These results suggest the coexistence of two types of antitumor cytotoxic lymphocytes at the tumor site: precursors of NK-like cells and specific cytotoxic T cells. Target cell specificity provided a means of distinguishing between the two types.

Experimental studies on the mechanism of induction of anti-nuclear antibodies by procainamide☆

Abstract The occurrence of anti-nuclear factor (ANF) following immunization with procainamide (PrA) conjugates, reactions in vitro between PrA and nuclear components, and the effect of PrA on the immune response to soluble nucleoprotein (SNP) and DNA were examined. Conjugates of PrA with protein elicited formation of antibodies towards PrA in rabbits and guinea pigs without the appearance of ANF even after prolonged immunization. PrA reacted with SNP by forming a precipitate containing PrA and non-dissociated SNP. DNA alone or histone was not precipitated by PrA. PrA also bound to isolated mouse liver nuclei. Aggregates of PrA with SNP and a conjugate of PrA with DNA elicited an immune response to both PrA and DNA in rabbits and guinea pigs. A conjugate of azobenzenearsonate prepared in a similar way induced an immune response against the hapten only, without development of anti-DNA antibodies.

The prevalence of antibodies to histones induced by procainamide in old people, in cancer patients, and in rheumatoid-like disease.

Antibodies to histones were found to be most commonly responsible for the positive antinuclear antibody (ANA) test in asymptomatic patients treated with procainamide, in old people, in patients with neoplastic diseases, and in young women affected with a rheumatoid-like disease. Only in a very few patients were antibodies to dDNA and nucleoproteins demonstrated. Antibodies to nDNA were not found. The antibodies to histones were demonstrated by two methods: absorption of ANA-positive sera with a histone solution and subsequent performance of an ANA test; and acid elution of histones from thyroid sections followed by histone reconstitution.

Angioimmunoblastic lymphadenopathy with paraproteinemia: A T- and B-Cell disorder

A case is reported of angioimmunoblastic lymphadenopathy (AILD), in which a IgM Kappa monoclonal gammopathy developed. On the first admission the immunoblasts were shown to be T cells by surface‐marker studies. Although the number of circulating T cells was normal, their functional capacities were markedly reduced. The patient was followed for two months at the end of which she died with hematologic features of immunoblastic plasma cell leukemia.

Inhibition of delayed hypersensitivity reactions in mice by colchicine: I. Mechanism of inhibition of contact sensitivity in vivo

Colchicine has been recently shown to inhibit delayed hypersensitivity reactions (DHR). In the present study we investigated the effects of colchicine on contact sensitivity (CS) to dinitrofluorobenzene. Colchicine, at a dosage level of 15 micrograms/mouse, inhibited the elicitation of the contact response only when given on the day of ear challenge. Administration of the drug during the induction phase did not have any effect on the CS reaction. By using adoptive transfer experiments, we could demonstrate that CS was suppressed only when colchicine was given to the recipient mice, while treating the donors of immune lymph node cells (I-LNC) did not affect their ability to transfer a significant DHR. These findings were observed also when I-LNC were directly injected into the ears, a result which indicated that there was no effect of the drug on the ability of effector cells to migrate to the site of antigen challenge. Neither was there any effect on the distribution of T cell subsets in peripheral lymph nodes. The proliferative response of LNC to antigenic or mitogenic stimulation in vivo or in vitro was also not affected by colchicine pretreatment. These findings raise major questions about the mechanism of action of colchicine in vivo and suggest that more experimentation is required to probe the mechanism of colchicine-induced suppression of DHR.

Circulating immune complexes in sera from patients receiving procainamide

Abstract Sera from patients receiving procainamide (PrA) therapy were investigated for their ability to inhibit an antibody-dependent cell-mediated cytotoxicity system (ADCC). Before the start of therapy 1 out of 20 sera from patients were inhibitory. Two months following the onset of therapy, 21 out of 29 sera (72%) inhibited ADCC. Sera from 13 out of 29 (44%) patients receiving PrA for periods greater than 6 months still displayed inhibitory factors. The inhibitory factors were found by sucrose-gradient ultracentrifugation to be located mainly in fractions 7 S to 19 S. Adsorption of sera with anti-human IgG linked to Sepharose removed inhibitory factors whereas similar treatment with anti-human IgM Sepharose did not, indicating that IgG was present in the inhibitory material. These results are consistent with the hypothesis that PrA induces IgG-containing immune complexes.

Malignant thymoma with peripheral blood lymphocytosis

A 37‐year‐old woman with a giant, lymphocytic predominant thymoma involving the pleura and accompanied by a sharp peripheral blood lymphocytosis is described. Only electromicroscopic and immuno‐histologic studies could exclude the alternative diagnosis of mediastinal lymphoma. The tumor and peripheral blood lymphocytes were characterized as T4 lymphocytes. The thymoma responded very well to a combination of radiation and cytotoxic therapy. Forty‐two months after diagnosis, the patient is still is complete remission.

Procainamide-induced antibodies to nucleoprotein, denatured and native DNA in human subjects

Abstract Distribution of antibodies reacting with nucleoprotein, denatured and native DNA in sera of procainamide-treated patients was determined by the counterelectrophoresis and passive hemagglutination methods. Differences among the sera were dound according to their ability to react either with both NP and DNA or only with NP or DNA preparations. Nonspecific reactions of unheated human sera with denatured and native DNA were detected. These reactions werd partially abolished by heat inactivation of sera.

Augmentation of mitogen responsiveness in the aged by a special lipid diet AL 721

Diminished immune responses in aging may be partially due to alteration of the lipid composition of membrane and a decrease in membrane fluidity. The effect of a daily diet of 10 g active lipid (AL 721) on the mitogen responsiveness of peripheral blood mononuclear cells (PBMC) from aged volunteers was studied. AL 721 is a mixture of lipids from hen egg yolk which was formulated for in vivo rectification of rigidified cell membranes in an attempt to restore proper physiological function. After 3 weeks on the diet, six aged participants displayed a significant increase in lymphocyte responsiveness to mitogens, while in four the responsiveness was unaffected, or increased insignificantly. In all six participants, a decline in lymphocyte responsiveness was observed a week after termination of the diet. Our preliminary results indicate that improvement of immune functions in the aged may be achieved by dietary manipulation of lipids. This innocuous approach seems to be of potential value and merits further studies.

Kaposi's sarcoma and angioimmunoblastic lymphadenopathy

Kaposis sarcoma (KS) and angioimmunoblastic lymphadenopathy (AILD) are exceptionally rare neoplastic diseases, although the former has recently been more frequently reported among certain populations, and is lately a topic for extensive medical and investigational interest. This case is unique in that it describes an association between KS and AILD. Such an association raises the question of a common pathogenic mechanism. The authors believe that predisposition to each of both diseases may be related to acquired immune deffiency which in turn may be induced by specific viral infections.