Effect of mannose-binding protein on binding of Cryptococcus neoformans to human phagocytes.

The capacity of human peripheral blood monocytes, neutrophils, and monocyte-derived macrophages to bind the yeast Cryptococcus neoformans was increased when the phagocytes were cultured on surfaces containing recombinant human mannose-binding protein. In contrast, soluble mannose-binding protein had no effect on cryptococcal binding by phagocytes.

Biological activity of interleukin-2 bound to Candida albicans.

The lymphokine interleukin-2 (IL-2), which is necessary for the generation of an optimal cell-mediated immune response, has recently been shown to have lectinlike properties, with specificity for high-mannose groups. Therefore, the ability of IL-2 to bind to the mannose-rich fungus Candida albicans was examined. Heat-killed fungi preincubated with IL-2 stimulated, in a dose-dependent manner, proliferation of the IL-2-dependent cell line CTLL20. Soluble mannan, which is rich in exposed mannose groups, inhibited binding of IL-2 to C. albicans by approximately 60%, suggesting that the lectinlike properties of IL-2 are partially responsible for its fungal binding capacity. Binding of IL-2 to fungi appeared to be reversible, as C. albicans preincubated with IL-2 stimulated CTLL20 proliferation even when the fungi and cells were separated by an 0.4-microns-pore-size membrane. The lymphoproliferative response of normal human peripheral blood mononuclear cells to C. albicans was augmented when the fungus was preincubated with IL-2. Binding of 125I-IL-2 could not be inhibited by unlabeled IL-2, suggesting the absence of high-affinity receptors on C. albicans for IL-2. While the in vivo relevance remains to be determined, these data demonstrate that IL-2 can bind to C. albicans in vitro and thereby influence the host response to this medically important fungus.

Fungal meningitis.

Fungal meningitis tends to be a subacute or chronic process; however, it may be just as lethal as bacterial meningitis if untreated. There are many similarities between the pathogenic fungi. Most of the fungi are aerosolized and inhaled, and initiate a primary pulmonary infection which is usually self-limited. Hematogenous dissemination may follow the initial infection, with subsequent involvement of the CNS. Rarely, trauma or local extension provides the route to CNS infection. The host is frequently, although not always, immunosuppressed. The hyphae of molds generally cause focal disease with hemorrhagic necrosis secondary to vascular thrombosis. The yeasts tend to cause a more diffuse process with the base of the brain being primarily affected, such that hydrocephalus is seen as a frequent complication of chronic disease. Diagnosis may be difficult, as the CSF may be normal, with negative smears and sterile cultures, although more often there is at least one abnormality indicating disease. Serologies (if available, depending on the fungus) may point towards the proper diagnosis, as may a careful travel history. Currently, amphotericin B is still the drug of choice in most situations; however, the newer azole antifungal agents offer great promise, especially in the treatment of cryptococcal meningitis. The precise role of such agents will remain unclear until appropriate large-scale studies of their effectiveness have been completed. The treatment of the unusual CNS mycoses will continue to be based on clinical experience, and reports of the use of new azoles in these diseases need to be critically evaluated.

Cellular immunity to heterotopic corneal allografts in the rat.

Although the immune nature of corneal allograft rejection has been recognized for over thirty years, the specific mechanisms involved in such reactions remain obscure. We investigated the cellular immune responses of PVG (RT1c) rats that were grafted with fully allogeneic ACI (RT1a) skin, ACI cornea, or PVG cornea to the chest wall or given sham grafts. Cell-mediated lymphocytotoxicity (CML) was tested at 10 days posttransplant by placing recipient spleen cells in culture with irradiated ACI stimulator cells, and six days later measuring specific lysis of 51Cr-labeled target lymphoblasts at several effector-to-target ratios. Effector cells from animals receiving allogeneic skin or cornea grafts lysed targets from the donor (ACI) strain at levels significantly (P less than 0.01) above those obtained using effectors from control (sham grafted or syngeneic corneal graft recipient) animals. Significant lysis was also seen using target cells from PVG.1A (RT1a) or PVG.R1 (RT1r1) congenic rats, which differ from recipients only at the RT1 complex and the RT1.A (class I antigen) region, respectively. Stimulator cells from PVG.1A and PVG.R1 animals also permitted detection of specific responses in secondary CML, but syngeneic PVG stimulators did not, indicating that in vitro restimulation of effector cells can be met by using stimulator cells bearing only allogeneic class I major histocompatibility complex (MHC) antigens. These results indicate that corneal allografts evoke specific cellular immune responses in the rat, and that class I MHC antigens act as effective targets for these responses.