Delineation of suppressor and helper activity within the OKT4-defined T lymphocyte subset in human newborns.

Lymphocytes taken from the cord blood of newborns have active suppressor activity. Using in vitro PWM-stimulated cocultures, unfractionated T cells from newborns potently suppressed the expected immunoglobulin G (IgG) synthesis of their mothers' peripheral blood lymphocytes (PBL). Using positive and negative selection techniques, we characterized the active suppressor cell as expressing the OKT4+T8- phenotype. This cord blood lymphocyte subset suppressed maternal IgG synthesis after depletion of maternal suppressor cells, implicating the ability of newborn T cells to suppress directly rather than by inducing adult suppressor activity. Sublethal amounts (1500 rad) of gamma-irradiation fully abrogated the suppressor activity of cord blood T lymphocytes. Radioresistant cord T cells provided T cell help. Irradiation of cord OKT4+ and OKT8+ populations and their subsequent culture with maternal B cells determined that helper activity was a radioresistant subpopulation of the OKT4+ subset. These results indicate significant differences in the functional properties of T cell subsets from adults and newborns. Population studies determined that cord blood lymphocytes had a greater proportion of OKT4+ cells and lower proportion of OKT8+ cells than PBL from unrelated adults. The mothers tested had similar proportions of OKT4+ cells as their babies, and these levels are significantly higher than those of unrelated adults.

Pathogenesis of experimental allergic orchitis. III. T lymphocyte requirement in local adoptive transfer by peritoneal exudate cells.

In experimental allergic orchitis (EAO), a lesion characterized by mononuclear invasion of seminiferous tubules can be adoptively transferred within 1 to 4 days by testicular injection of peritoneal exudate cells (PEC) from syngeneic strain 13 guinea pigs (GP) immunized with homologous testicular antigens in complete Freund's adjuvant (CFA). This study examined the role of T lymphocytes, macrophages, and polymorphonuclear neutrophils (PMN) in the adoptive transfer. Guinea pig PEC contained 7% T lymphocytes, rare B lymphocytes, and over 90% of macrophages and PMN. After T lymphocytes were depleted by rabbit erythrocyte (E) rosette and Hypaque-Ficoll gradient centrifugation, cell preparations that contained 73% of original macrophages and 15% original T lymphocytes were obtained, and these cells did not transfer EAO (0 of 18 testes). In contrast, cell preparations enriched in T lymphocytes by nylon wool column or E rosette contained 1.5% of the original macrophages and 59% of the original T lymphocytes transferred EAO to 70% of the testes, starting at 1.5 x 10(6) T lymphocytes per testis. The number of T lymphocytes correlated with the incidence of adoptive transfer; the correlation existed regardless of the number of macrophages or PMN present. Finally, EAO was adoptively transferred to recipients that had total-body irradiation. The results indicate that (a) T lymphocytes are capable of transferring lesions of EAO, (b) in the transfer, the T lymphocytes did not function as helper T cells, since the transfer need not involve participation of host lymphoid cells, and (c) by inference, testis antigen-reactive T lymphocytes exist.

[Transmission of a delayed allergic reaction to Salmonella abortus-ovis via the blood plasma of gamma-irradiated guinea pigs]. / Prenasiane na alergichna reaktsiia ot zabaven tip sreshtu Salmonella abortusovis s kruvna plazma ot morski svincheta, oblucheni s gamma-luchi.

Use was made of blood plasma taken from guinea pigs (sensibilized with a live culture of Salmonella abortus ovis and then irradiated wiht 800 rad gamma-rays) to transmit the skin allergy reaction to normal, nonsensibilized guinea pigs. The allergy reaction was demonstrated in the recipients of plasma as early as the 3-4th hour following the injection of the allergen into the skin. It reached its peak at the 12-24th hour and later on strongly diminished, remaining in few of the animals only up to the 48th hour. The infiltrate at the site of injection in the skin of positively reacting animals contained at the 24th hour cells of the polymorphonuclear type which predominated, while the cells of the mononuclear type were few in number. There were no precipitins in the plasma of the donors, and the titer of the agglutinins and the cytophile antibodies was very low. Regardless of these findings it was concluded that the transmitted allergy reaction was of the fast type (after Arthuss), and not of the delayed one.

Contact sensitivity in the mouse. IV. The role of lymphocytes and macrophages in passive transfer and the mechanism of their interaction.

Contact sensitivity skin reactions were produced in mice by immunization with 2-phenyl-4-ethoxymethylene oxazolone (oxazolone) and detected by the increase in ear thickness after challenging the ears with 2% oxazolone. These skin reactions can be transferred from immunized donors to irradiated recipients by peritoneal exudate cells induced by thioglycollate. The peritoneal exudate cells were separated into purified macrophage and purified lymphocyte populations. Both cell populations transferred skin reactions. However, their time course was different. The reactions produced by lymphocytes were greater at 24 hr than at 12 hr while the reactions produced by macrophages declined slightly between 12 and 24 hr. The working hypothesis was formed that the peritoneal lymphocytes conveyed a factor (presumptive cytophilic antibody) to peritoneal macrophages which enabled them to transfer ear reactions. Experiment showed that peritoneal and lymph node lymphocytes from sensitized donors within a Millipore chamber conveyed a factor to macrophages outside the chamber which enabled them to transfer ear reactions. In contrast, peritoneal macrophages (from sensitized donors) within the chamber and peritoneal lymphocytes outside the chamber were inactive. These findings suggested that there are three modes of immunological tissue damage: hypersensitivity mediated by lymphocytes (classical delayed hypersensitivity), hypersensitivity mediated by circulating antibody (classical immediate type hypersensitivity), and hypersensitivity mediated by macrophages which have passively acquired a factor (macrophage-mediated hypersensitivity).

The effect of cytotoxic agents on the passive transfer of cell-mediated immunity.

A system involving the passive transfer of committed lymphoid cells from Listeria-immune donors has been used to study the phases of the immune response which are sensitive to the immunosuppressive action of various cytotoxic agents. The agents investigated included cyclophosphamide, vinblastine, methotrexate, azathioprine, and X-irradiation. Complete suppression of passive immunization was obtained by the administration of cyclophosphamide or vinblastine to recipients at the time of cell transfer or by prior X-irradiation of recipients a day before cell transfer. Methotrexate was only partially suppressive, whereas azathioprine had no effect at all. The donor cell responsible for the transfer of immunity to recipients was shown to be a resting cell which is sensitive to the action of cyclophosphamide but not to vinblastine. The results of this investigation suggest that the donor cells undergo multiplication in the tissues of the recipient, presumably in response to specific stimulation by Listeria antigens. This in turn results in the activation of host macrophages. The immunosuppressive action of cyclophosphamide, vinblastine, and irradiation in the cell-transfer system has been discussed in relation to a direct cytotoxic action on the immune lymphoid cells of the donor and specific interference with their proliferation in the recipient, as well as impairment of macrophage production on the part of the recipient itself.