A further characterization of Candida albicans-induced suppressor B-cell activity.

We have previously established that components of the organism Candida albicans are capable of inducing suppressive activity in a population of B lymphocytes. The activity of this population is antigen non-specific. The proliferative response to T-cell, but not B-cell, specific mitogens is inhibited. In addition, the antibody response in vitro is suppressed. Since little is known about this relatively unique regulatory population, we have attempted to characterize both the expression and induction of activity of the Candida-primed cells. Our results show that both primary and secondary T-cell-dependent antibody responses are inhibited, whereas both type I and type II T-cell-independent antibody responses are not affected by the suppressor cell population. T-cell populations responsible for both interleukin-2 (IL-2) and cytolytic activity are also unaffected. These results suggest that while there is no antigen specificity for this population, the suppressive activity is extended to limited target cell populations. Results also suggest that both T cells and accessory cells are required for the induction of the suppressor cell activity, indicating that the Candida organism acts as a typical T-dependent antigen in the induction of regulatory cell activity.

Plasmodium berghei malaria: effects of acute-phase serum and erythrocyte-bound immunoglobulins on erythrophagocytosis by rat peritoneal macrophages.

Acute-phase serum (APS) collected from Plasmodium berghei-infected rats inhibited phagocytosis of trypsinized rat erythrocytes and of erythrocytes from P. berghei-infected rats. Macrophages (M phi) incubated with APS or heat-aggregated acute-phase serum (HAAPS) for 6 h, followed by 18 h incubation in serum-free medium, exhibited significantly higher levels of phagocytosis than M phi similarly cultured but with normal rat serum. When APS was present at the time of assay, it inhibited erythrophagocytosis by M phi which had been in culture for 0 or 24 h. M phi activation by HAAPS was inhibited by 2-deoxy-D-glucose, which suggests that activation by HAAPS is Fc-receptor mediated. Adsorption of APS with staphylococcal protein A abrogated the ability of APS to inhibit phagocytosis and that of HAAPS to effect M phi activation, suggesting that immune complexes are involved in both processes. Surface-bound immunoglobulins eluted from erythrocytes of P. berghei-infected rats promoted phagocytosis of trypsinized erythrocytes by HAAPS-activated M phi but not by resting M phi. These results indicate that the immunoglobulins which bind to infected or damaged erythrocytes during malarial infections promote erythrophagocytosis by activated M phi and that the immune complexes in serum from rats with acute malaria may inhibit erythrophagocytosis early in the infection but may, over time, induce changes in the M phi which later facilitate erythrophagocytosis.

Plasmodium berghei: characterization of antigens and their role in inducing immunity to infection.

In vitro, Plasmodium berghei infected erythrocytes incorporated 35S-methionine into 31 polypeptides with molecular weights from 21 kd to 300 kd. Hemoglobin and additional smaller molecular weight polypeptides were labelled with 35S-methionine by a population of uninfected, reticulocyte-rich rat erythrocytes. 3H-glucosamine was incorporated into at least 3 components by Plasmodium berghei infected erythrocytes. Uninfected, reticulocyte-rich rat erythrocytes did not incorporate 3H-glucosamine. Rabbit antisera against small, free plasmodia formed complexes which contained between 12 and 22 of the 31 labelled polypeptides in the 35S-methionine labelled antigen preparation. Rabbit antisera against soluble antigens washed from small, free plasmodia formed complexes containing many of the same labelled plasmodial polypeptides, however the reactions were particularly strong with those components which yielded polypeptides with molecular weights of 25 kd and 31 kd. Rabbit origin antisera against the 2 preparations did not form detectable complexes with the 3H-glucosamine labelled plasmodial components. Sera from rats undergoing progressive P. berghei infection formed complexes containing an increasing number of 35S-methionine labelled plasmodial polypeptides. Hyperimmune rat serum, the only serum protective upon passive transfer into mice, formed complexes containing 7 polypeptides with molecular weights of 35 kd, 75 kd, 80 kd, 92 kd, 100 kd, 150 kd and 190 kd. Antigens containing 1 or more of these polypeptides may be important in the induction of a protective antibody response against the parasite.

A role for rheumatoid factor enhancement of Plasmodium falciparum schizont inhibition in vitro.

Studies were undertaken to determine whether rheumatoid factor (RF) was present in immune human and Aotus trivirgatus monkey sera which inhibited Plasmodium falciparum schizonts in vitro and to determine whether RF could be responsible for or contribute to merozoite agglutination in the parasite inhibition test. Additional studies were conducted to determine the effect of exogenous RF on schizont inhibition when used alone or in conjunction with immune or normal sera. RF was not detected in any of the 11 immune monkey sera or the 3 immune human sera which were tested. However, when RF was added to immune human or Aotus sera, levels of schizont inhibition increased significantly over levels obtained with immune serum alone. When RF was used alone or in conjunction with normal sera, levels of schizont inhibition were comparable to those obtained with normal serum. Furthermore, adsorption of the RF with immunoglobulin G-coated erythrocytes removed the enhancing activity. The results of this study indicate that RF, which is sometimes produced during acute or chronic malarial infection, may contribute nonspecifically to the enhanced clearance of plasmodia in vivo.

The effects of lipopolysaccharide, BCG-immune T lymphocytes, and lymphokines on generations of tumoricidal pulmonary macrophages in Syrian hamster.

Bacterial lipopolysaccharide (LPS) stimulates pulmonary macrophages from BCG immune-rechallenged hamsters to kill tumor cells in vitro. However, pulmonary macrophages from BCG immune and from untreated hamsters cannot be activated for tumor cytotoxicity by in vitro treatment with LPS. Pulmonary macrophages from the nonimmune hamsters acquire tumoricidal capacity after 3 hr of coculture with T cells from BCG immune-rechallenged hamsters or when incubated with Con-A-stimulated spleen cell supernatant fluid. A heterogeneous population of pulmonary lavage cells from BCG immune and from BCG immune-rechallenged hamsters destroys the tumor cells more effectively than a homogeneous population of pulmonary macrophages from the same animals. LPS significantly augments the cytotoxic activity of the heterogeneous population of pulmonary lavage cells.