Subpopulations of human T lymphocytes. V. T lymphocytes with receptors for immunoglobulin M or G in patients with primary immunodeficiency disorders.
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Biomedical subjects
Publications and source records attributed to R A Good.
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Cellular and humoral components of leukotaxis were studied serially in four male infants with severe combined immunodeficiency disease. Two of the four, both lacking B and T cells initially, had a significant defect in neutrophil and monocyte chemotaxis. The other two, who had a high number of immunoglobulin-bearing cells (B cells), did not have these cellular abnormalities. It contrast, defective generation of chemotactic factor following endotoxin activation was observed in all patients. The defects were corrected coincident with or soon after successful engraftment of either bone marrow or fetal tissues. The reported deficiencies may be another manifestation of the heterogeneity in SCID.
Human peripheral blood non-T cells, T cells and their subpopulations (Tmu, Tgamma, Tphi, Tgamma-depleted cells, and Tmu-depleted cells) were assayed for their capacity to mediated spontaneous lymphocyte-mediated cytotoxicity (SLMC) or natural killer activity against K562 tumor cell line and antibody-dependent cellular cytotoxicity (ADCC) against chicken erythrocytes coated with antibody. Non-T cells, unseparated T cells, Tgamma cells, and Tmu-depleted (Tgamma-enriched) cells were found to have both SLMC (NK activity) and ADCC. Tmu, Tphi, and Tgamma-depleted cells had minimal or no SLMC and ADCC activity. This study demonstrates that SLMC and ADCC activity in T cells is mediated by Tgamma cell subpopulations. These two cytotoxic reactions were either mediated by two distinct subsets of Tgamma cells or by a single effector cell using two different mechanisms.
In (NZB x NZW)F(1) (B/W) mice, moderate caloric intake [10 kcal (41.8 kJ) per day] from the time of weaning was associated with maintenance of lower body weight, greater capacity of spleen cells to be stimulated with T-cell mitogens, and better preserved capacity to generate cytotoxic cells in response to in vitro and in vivo stimulation with allogeneic tumor cells. Plaque-forming cell response to sheep erythrocytes was also well maintained in animals on the restricted diets when sensitization was accomplished either in vitro or in vivo. Spontaneous suppressor cell activity against plaque-forming cells that developed in controls did not appear in the mice on the restricted diet. Significantly less circulating antibody to native DNA was present in the blood of mice 10 months of age when their dietary intake had been restricted. Histological analysis revealed that the development of renal disease and the deposition of gamma globulin in the glomerular capillaries was markedly inhibited in the mice on restricted diets. Dietary restriction from the time of weaning thus appears to prolong significantly the life of autoimmunity-prone (NZB x NZW)F(1) male and female mice and to alter lymphoid cell immune function, thereby decreasing the autoimmune processes and immunological assault associated with progressive renal disease in these animals.
Human peripheral blood lymphocytes are stained with the metachromatic dye acridine orange and the fluorescence of individual cells is measured by flow cytometry. The relative content of stainable RNA per cell is estimated by comparison with RNase-treated cells. Non-T and T lymphocytes have different mean quantities of RNA per cell, and these classes exhibit different distributions of RNA content. Non-T cells have a unimodal distribution with a sharp peak and exponential distribution towards higher RNA values. T cells have a bimodal distribution with two separate peaks. When T cells having receptors for IgG (Tgamma cells) and IgM (Tmu cells) are separated, each of these cell populations displays a unimodal distribution. Of these three lymphocyte subpopulations, Tgamma cells have the lowest content of RNA per cell. Non-T cells have slightly higher RNA content than Tgamma, and Tmu cells have twice as much RNA as Tgamma cells. The RNA content, which surely relates to the different functions of these lymphocyte subpopulations, may also be a useful marker for rapidly distinguishing the lymphocyte subpopulations.
Locomotor activity of T cells with receptors for IgM and IgG, T cells without receptors for IgM or IgG, and T and non-T cells from human peripheral blood and human tonsils towards the chemoattractant casein was examined in modified Boyden chambers. T cells with receptors for IgG both from human tonsils and peripheral blood did not move in response to casein. T cells with receptors for IgM and those without receptors for IgM or IgG, on the other hand, moved very well toward casein and the distances were comparable to those achieved by T cells before separation. This difference in the locomotor activity of T cell subsets might explain their differential distribution in various lymphoid compartments. Separated T cells, cultured in medium supplemented with fetal calf serum, moved into the filters in response to casein. Prior culture of T cells in medium alone or in medium supplemented with human AB serum resulted in a reduction in the distance traveled in response to casein; however, the effect of AB serum was variable. Non-T cells from peripheral blood and B cells from tonsils responded poorly to casein.
Striking inhibition of development of renal disease and prolongation of lifespan have been achieved in kdkd mice by restricting their daily food intake. Restricting protein intake alone did not prolong life nor did it inhibit development of kidney disease. The kdkd nephronophthisis, although very different histologically from the renal disease of B/W mice, may also have immunological components. Like the immunologically based renal disease of B/W mice, renal disease in kdkd mice is decreased or eliminated histologically by dietary restriction, which inhibits development of autoimmunity directed toward the erythrocytes of these mice. Further analysis will be needed to elucidate the cause of progressive renal disease in both the kdkd and B/W models and to permit understanding of the profound influence of restriction of food intake on development and progression of these very different renal diseases.
Twenty-two patients with selective IgA deficiency were studied for the presence of serum precipitins to bovine milk, bovine and fetal calf serum, and circulating immune complexes. Fifty-nine percent had circulating immune complexes, 50% had milk precipitins, 23% had precipitins to bovine serum, and 13% had precipitins to fetal calf serum. All patients with precipitating antibodies against milk or against bovine or fetal calf serum had circulating immune complexes and the precipitin titers correlated with the amount of circulating immune complexes. After one IgA-deficient patient had drunk 100 ml of milk, studies of sequential serum samples showed the presence of casein in the circulation at 60 min and the appearance of increasing amounts of immune complexes for 120 min. These findings are interpreted to indicated that in human beings the IgA system may provide a major barrier to absorption of immunogens from the gastrointestinal tract.
The covalently binding fluorescent probe 5-dimethylamino-1-naphthalenesulfonyl (dansyl) chloride was affixed directly to the plasma membrane of viable human peripheral blood lymphocytes via a solid phase transfer method utilizing Sephadex G-10 as the transfer vehicle. After dansylation, lymphocytes retain maximal short-term viability. Dansyl, as the protein conjugate or as the free acid, does not appear to penetrate the cells to any significant extent. Dansylated mixed lymphocyte cultures respond to lectin mitogen stimulation for at least 72 hr. Furthermore, differential response of dansylated lymphocytes in culture to three plant lectin mitogens provides a clue to the binding loci of concanavalin A with respect to phytohemagglutinin and pokeweed mitogen on the lymphocyte surface receptors for these lectins. The ability to sustain functionally responsive dansylated lymphocytes for several days in culture suggest that such probe-tagged cells may be useful in elucidating aspects of the plasma membrane in the regulation of cell behavior.
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Skin changes may be the first clue to a neoplastic process at a stage when it still is treatable (Such as the development of Acanthosis Nigrican (AN) in an otherwise healthy adult). Ninety percent of the neoplasm responsible for the development of AN originate in the abdomen. The tumor, even in a subclinical state, seems to possess unidentified properties that activate the dermatosis.
The presence of circulating immune complexes (ICS) in freshly drawn sera of 67 children with neuroblastoma was studied by the Raji cell radioimmunoassay of Theofilopoulos et al. (J. Clin. Invest. 57: 169--182), with particular emphasis on the correlation of levels of ICS with stage of disease and changes attributable to treatment. There was a close correlation between amount of complexes and stage of disease and treatment. Levels of ICS increased as the stage of the disease advanced, and were significantly higher (P less than 0.005) in stage IV than in all other stages combined. When patients with stage IV disease were subdivided into "before," "during," and "after" treatment groups, there was a significant decrease in ICS levels as treatment progressed. Studies of complement and complement components did not give such a clear relationship. A significant decrease of hemolytic C1 values was found in patients with "active disease" compared to normal age-matched controls. Some high C3 levels, determined immunochemically, were associated with low hemolytic levels of C3, which were attributed to C3 cleavage detected by immunoelectrophoresis. Based on our survival data, ICS, which were significantly different in 20 patients now decreased when compared to those of other patients, are very valuable in the prognosis of neuroblastoma.
A study of peripheral blood lymphocyte populations in 27 children with Hodgkin's disease (HD) and 13 age-matched control subjects is presented. The absolute numbers and percentages of T and B lymphocytes identified by their surface marker characteristics were determined. In addition, in 13 HD children the percentages of T and B lymphocytes were estimated in the spleens removed at staging laparotomy. No differences were observed between the total peripheral blood lymphocyte counts of HD and control children, and we found no evidence of progressive lymphopenia with advancing stages of the disease. No decrease in the numbers of peripheral blood T lymphocytes was seen in this group of HD children. In contrast, the proportions and absolute numbers of B lymphocytes tended to be significantly lower in the children with HD than in the control subjects. In 9 of the 13 spleens studied high percentages of T lymphocytes were seen; low percentage of B lymphocytes were found in all spleens examined.
Circulating thymic hormone activity and thymic histology were studied in patients undergoing open heart surgery. Plasma thymic hormone activity was measured using a bioassay based upon thymocyte antigen induction on null mouse lymphocytes. Activity was highest at 15-30 yr of age and declined thereafter, being negligible after the sixth age decade. The age-related decline of circulating thymic hormone activity correlated, in general, with progressive thymic involution. However, hormone activity was detected in plasma from some cases with advanced involution, suggesting that the normal young thymus may have considerable functional reserve.
Fifty-four patients with epidermoid head and neck cancer were studied with routine and modified mixed leukocyte culture (MLC) techniques to quantify and characterize their cell-mediated immunity (CMI). Of these, 67% demonstrated deficient CMI in MLC. Employing G-10 column filtration to remove adherent cells selectively, the authors found that 56% of these deficient individuals demonstrated significantly increased lymphocyte responsiveness in MLC. Returning the adherent cells to the cultures usually recaptured the suppressive effect of these adherent cells. Cell marker analyses reveal that the macrophage is the most likely candidate for this suppressive cell. Therapeutic measures which address this paradoxically suppressive cell could be of benefit in enhancing CMI and gaining tumor control.