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Biomedical subjects

D T Yu

Publications and source records attributed to D T Yu.

At least 19 recordsLinked to original sources

Ia determinants on stimulated human T lymphocytes. Occurrence on mitogen- and antigen-activated T cells.

Human T-cell blasts were generated by stimulation with mitogens and antigens. A proportion of these blasts expressed Ia antigens detectable by immunofluorescence with both allo- and hetero-antiserums. The maximal expression of Ia antigens was delayed and usually occurred after the peak of blastogenesis. Among the three mitogens used, pokeweed mitogen (PWM) was most effective in giving a high percentage and intense Ia staining of T-cell blasts. Phytohemagglutinin and concanavalin A blasts gave weaker and lower percentages of Ia staining. Activation by alloantigens and soluble antigens such as tetanus toxoid and purified protein derivative resulted in Ia expression on T cells comparable to PWM stimulation. Depletion of Ia+ cells from freshly isolated T cells with anti-Ia and complement decreased subsequent Ia expression, suggesting that a proportion of Ia+ blasts were derived from Ia-bearing peripheral blood T cells. When the specificities of the Ia antigens on T-cell blasts were examined with alloantiserums, it was evident that the T blasts expressed similar HLA-DR determinants to those on B cells from the same donor; occasional minor differences between stimulated T cells and autologous B-cell lines or fresh B cells were encountered.

Cells, Cultured

Glucocorticoids administered in vivo inhibit human suppressor T lymphocyte function and diminish B lymphocyte responsiveness in in vitro immunoglobulin synthesis.

The effects of corticosteroid given in vivo on human lymphocyte subpopulation function were investigated using an in vitro system of pokeweek mitogen-stimulated immunoglobulin production. Peripheral blood lymphocytes were obtained from normal volunteers before and 4 h after the intravenous administration of methylprednisolone. Unfractioned peripheral blood lymphocytes showed a consistent decrease (mean congruent with 50%) in immunoglobulin and total protein synthesis after steroid administration. Utilizing separated thymus-derived (T) and bone marrow-derived (B) lymphocyte fractions, the pathophysiology of this alteration in immunoglobulin production was elucidated. B lymphocytes obtained after steroid treatment showed a markedly diminished immunoglobulin response (20% of normal) to normal T lymphocytes and to normal T cells that had been irradiated to remove suppressor T lymphocyte function. All major classes of immunoglobulin (IgG, IgM, and IgA) were affected. T lymphocytes procured after steroid administration were capable of providing normal amounts of T cell help for B cells in immunoglobulin production. However, suppressor T lymphocyte activity, observed with normal T lymphocytes at high T to B cell ratios, was absent from the post-steroid T lymphocytes. This loss of suppressor T lymphocyte function was not due to the presence of excess help as irradiated pre- and poststeroid T cells provided equal amounts of helper activity. On recombining the poststeroid treatment B cells, which are hyporesponsive in immunoglobulin synthesis, with the posttreatment T lymphocytes, which lack suppressor activity, diminished amounts of immunoglobulin were produced which correlate well with the effects observed with unseparated cells. Thus, corticosteroids have differential effects on the lymphocyte populations involved in immunoglobulin biosynthesis. B cell responsiveness is diminished, suppressor T lymphocyte activity is removed, and helper T lymphocyte function is unaffected.

Adult

Cellular collaboration in the production of human leucocyte migration inhibition factor.

The participation of cell subpopulations in the expression of leucocyte migration inhibition factor (LMIF) in response to Concanavalin A and Protein A was evaluated for cells isolated from the peripheral blood of five healthy subjects. LMIF activity could not be attributed to the function of T cells, B enriched cells, or monocytes acting alone, or to a combination of B enriched cells and monocytes. The LMIF response was the result of a collaborative event that occurred between T cells and B enriched cells, or between T cells and monocytes.

B-Lymphocytes

Effect of corticosteroids on committed lymphocytes.

Human peripheral blood lymphocytes were cultured for 48 hr with concanavalin A. The amount of [3H]thymidine incorporated during the last 4 hr of culture, as well as the percentage of rosettes of activated lymphocytes generated, were assayed at the 48th hr. Adding 0.1 M alpha-methyl-D-mannoside (MAM) at progressively later times after the initiation of culture caused progressively less suppression because of the commitment phenomenon. This suppression was not exceeded by the addition of 10(-4) M preparations of corticosteroids and was statistically the same as that induced by a combination of both corticosteroids and MAM. The addition of PGE2 alone and in combination with methylprednisolone also failed to affect [3H]thymidine incorporation by committed lymphocytes.

Adrenal Cortex Hormones

Effect of corticosteroids on the human immune response: comparison of one and three daily 1 gm intravenous pulses of methylprednisolone.

In spite of the increasing use of single and multiple pharmacologic intravenous pulses of MPS for immunosuppression in various diseases, their immunosuppressive effects have not been documented. We treated two groups of six patients with classic RA unresponsive to conventional therapy with either one or three daily 1 gm intravenous doses of MPS and measured the immune response and clinical activity over 16 weeks. Lymphocytopenia with selective T lymphocyte suppression was noted 2 hr following each infusion, which was maximal at 6 hr with complete recovery 24 hr after each dose beyond which no lymphocytopenia or T lymphocyte depletion was seen. Preservation of skin test positivity to recall antigens such as PPD and histoplasmin, rise in antibody titers to the secondary antigens tetanus and typhoid, and primary antibody response to KLH were found in both groups after treatment. Serum gamma globulin concentrations were unchanged. Five of six patients receiving 3 doses and three of six receiving 1 dose had satisfactory improvement in clinical parameters, with maximal benefit seen within the first 4 days. Six patients still felt better at 4 weeks, and one patient in each group entered a clinical remission greater than 16 weeks. We conclude that higher and repeated doses of MPS caused neither greater lymphocytopenia nor more prolonged suppression of recirculating lymphocytes than the conventional oral doses. The clinical benefits stem from reduction of inflammation, and it is doubtful that pulse therapy by itself induced significant generalized immunosuppression.

Aged

Human lymphocytes subpopulations: rabbit red blood cell rosettes.

When human lymphocytes were incubated with rabbit red blood cells (RRBC) in vitro at 4 degrees C overnight, they adhered to form rosettes. 44 +/- 4.5% of thymocytes and o.7 +/- o.3% of peripheral blood lymphocytes (PBL) formed these rosettes. The rosette-forming cells (RFC) increased to 10--40% when the PBL were stimulated by mitogens. The increases were detected 4 h after culture and reached a maximum at 24 h, thus preceding significant increases in DNA syntheses. In another set of experiments, PBL were stimulated by a range of concentrations of each of 5 mitogens. The concentrations whick led to high DNA synthesis rates also generated high percentages of the rosettes. Lastly, PBL were activated by mitogens and the effect of inhibitors of DNA synthesis, protein synthesis and ATPase activity investigated. Only the latter could inhibit the generation of the RFC. In conclusion, 1y RRBC rosettes in mitogen stimulated human PBL were markers of activated lymphocytes, 2) the percentages of RFC could constitute a reliable index of mitogenic responses, and 3) this index was independent of the usual criteria of protein and DNA synthesis.

Adenosine Triphosphatases

Lymphocyte abnormalities in ankylosing spondylitis.

Peripheral blood T (SRBC rosette) and B (AgG- and C-receptor) lymphocyte subpopulations and responsiveness to phytohaemagglutinin (PHA) were assayed in 40 patients with ankylosing spondylitis and in 55 normal subjects. There was no significant difference in the lymphocyte concentrations or responsiveness to PHA between the two groups. However, the percentages of T lymphocytes were significantly lower in the patients irrespective of their HLA typing. This was probably due to an increase in the 'null' population since the percentages of both the AgG- and C-receptor cells were normal.

Humans

Human lymphocyte subpopulations: rosette formation with sheep, human and horse red blood cells.

Rosette formation between human lymphocytes and horse red blood cells could be promoted by a low pH medium, overnight incubation and a temperature of 4 degrees C. The percent of sheep, horse and human rosette-forming cells in the peripheral blood were 71.7 +/- 1.8, 30.5 +/- 2.8 and 28.3 +/- 3.4 respectively. However, their percentages in thymuses were 97.1 +/- 1.1, 91.4 +/- 2.4 and 89.0 +/- 3.4. Using preparations of isolated subpopulations, it was observed that the horse and human red cell rosette-forming cells were probably also "early" sheep red cell rosette-forming cells. Rosette formation with all three types of red blood cells were inhibited by a preparation of Fetuin-glycopeptide.

Animals

Effect of corticosteroids on exercise-induced lymphocytosis.

Eight subjects ran on a treadmill at 8 miles per hr for 10 min. All developed lymphocytosis with predominant effect on the B cells. This was repeated 5 hr after receiving 60 mg of Prednisone. The lymphocytosis of both T and B cells were suppressed. When this was repeated 2 hr after receiving Prednisone, only lymphocytosis of the T subpopulation was suppressed. It was concluded that corticosteroid administration could suppress entry of lymphocytes into the circulation, with preponderant effect on the T subpopulation.

Adult

Effect of corticosteroids on the response of lymphocytes to stimulation by galactose oxidase-modified lymphocytes.

Human peripheral blood mononuclear cell preparations, after treatment by neuraminidase plus galactose oxidase, stimulated untreated lymphocytes. The increases in tritiated thymidine incorporation in the responder lymphocytes were observed after 48 h of mixed cell cultures. Monocytedepleted lymphocyte preparations were equally effective stimulator cells. Both purified T and B fractions were effective stimulator cells. On the other hand, only the T but not the B fractions could respond to the stimulation. The response of the cells to this type of stimulation was suppressed by 10(4)-10(7) M of the corticosteroid preparation methylprednisolone. When the cells treated with neuraminidase plus galactose oxidase were cultured alone for 48 h, they lost their stimulating capacity. However this loss could not be prevented by the presence in the culture of methylprednisolone. Hence the drug has selective suppressive activity on one type of lymphocyte activity but not the other.

Adrenal Cortex Hormones