In vivo effects of human dialyzable leukocyte lysate. III. Modulation of the spleen cell proliferative response to antigen by components of leukocyte dialysates and an initial characterization of an ampliative nucleoside.

The augmentative effects of isolated components of human dialyzable leukocyte lysates upon the proliferative response to antigen were investigated. Sequential Sephadex G-25 and Bio-Gel P-4 chromatography separated five distinct fractions which, 24 hr after injection into Keyhole limpet hemacyanin (KLH)-sensitive mice, either augmented or suppressed the in vitro spleen cell proliferative response to KLH. An amplifier molecule was isolated from one of the augmentative fractions by high-pressure, reverse-phase liquid chromatography. Preliminary structural analysis of the amplifier component indicated a nucleoside structure, similar to--but possibly distinct from--thymidine.

Serum IgE levels in healthy black American children: a case for environmental influences on IgE.

Serum IgE was determined in 115 healthy, non-atopic black American children, aged 0-16 years, living in Urban Chicago. The mean IgE level varied from 1.48 u/ml at birth to 70 u/ml at adolescence. These values are comparable to those observed in American whites but differ significantly from the IgE levels of both African blacks and European Caucasians. Thus, environmental factors apparently exert a strong influence on IgE production in non-atopic individual.

In vitro stimulation of natural killer (NK) cells by soluble factor(s) generated in antigen-stimulated rhesus monkey peripheral blood lymphocyte cultures.

Peripheral blood lymphocytes from rhesus monkeys (Macaca mulatta) sensitized to keyhole limpet hemocyanin (KLH), when stimulated in vitro with KLH, developed natural killer (NK) cell activity that was assayed with Rous Sarcoma virus-transformed marmoset fibroblasts as targets in a 4-hr 51Cr-release assay. The supernatant fluids from 24- to 25-hr KLH-activated cultures were capable of stimulating NK development in nonsensitive lymphocyte cultures. The effector cells were neither macrophages nor B cells (plastic and nylon-wool nonadherent) and did not form E-rosettes with neuraminidase-treated sheep red blood cells. Cultures depleted of EA-rosetting cells, i.e., Fc-receptor-bearing lymphocytes, were incapable of generating NK activity when stimulated in vitro. Kinetic studies showed that peak DNA synthesis, as measured by 3H-T incorporation, preceded maximum cytotoxicity. Elimination of dividing cells by 5-bromo-2'deoxyuridine (BrdU) and light treatment during the interval from day 1 to day 4 inhibited the development of cytotoxicity on day 7. Cell replication was required for the induction of NK cells with KLH as well as with antigen-activated culture supernatant fluids. When cultures were left unstimulated for 4 days, NK activity could not be developed subsequently either by adding antigen, mitogen (PHA), or supernatant fluids from activated cultures.

The in vitro suppression of antigen- or mitogen-induced DNA synthesis by murine spleen cells after the addition of freshly prepared syngeneic cells.

The suppression of antigen- and mitogen-induced DNA synthesis by murine spleen cells in vitro was investigated. It appears that cultures receiving two signals exhibit marked suppression of DNA synthesis. The addition of KLH, PPD, Con A, PHA, or LPS to 72-hr-lod cultures of KLH-stimulated murine spleen cells resulted in the suppression of DNA synthesis assayed at 144 hr. When small numbers of freshly prepared KLH-PPD SC or NSC were added to these cultures at 72 hr the suppression of DNA synthesis was abrogated. However, the addition of larger numbers of KLH-PPD SC or NSC resulted in increased suppression of DNA synthesis. Large numbers of KLH-PPD SC or NSC could substitute for the second stimulant (KLH, PPD, Con A, PHA, or LPS) in suppressing DNA synthesis. The addition of fresh cells obtained from KLH-PPD-immunized mice were more effective in eliciting the subsequent suppression than were cells obtained from non-immunized mice. Cells obtained 30 to 75 days post immunization were most effective in suppressing DNA synthesis.