Significance of Thymus-Derived Lymphocytes in Immunity Elicited by Immunization with Ribosomes or Live Yeast Cells of Histoplasma capsulatum

Abstract

The lymphoid cells responsible for protective immunity to histoplasmosis were characterized. Adoptive transfer of spleen and peritoneal cells treated with antiserum to theta-antigen from mice immunized with ribosomes or live yeast cells of Histoplasma capsulatum abrogated the ability of these cells to protect the syngeneic recipients, whereas treatment of lymphoid cells with antiserum to IgG did not affect the immunity. Prior removal of glass-adhering cells from spleen and peritoneal cell suspensions did not alter their protective activity. Treatment with mitomycin C, an antimitotic agent, ablated the capacity of immune lymphocytes to protect the syngeneic recipients. These results indicate that the immune spleen and peritoneal cells that confer immunity to histoplasmosis are thymus-dependent (T) lymphocytes and that their active proliferation in the recipients is necessary for expression of the protective immunity. Furthermore, the immunity elicited by immunization with histoplasma ribosomes and live yeast cells is mediated by a similar mechanism.

Production and Evaluation of Reagents for Detection of Histoplasma capsulatum Antigenuria by Enzyme Immunoassay

“…The intravenous immunization method used whole, formalin-killed H. capsulatum yeast-phase cells as the immunogen. This was the same immunogen employed to produce antibodies for use in the HPA-EIA test (29,42). The rationale for using C-Ag to screen rabbit antisera for use in our test was based on the following considerations.…”

“…Four rabbits were injected intravenously with 1 ml each of whole, killed H. capsulatum yeast-phase cells on days 0, 1,4,8,10,15,18,23,29, and 32. After day 56, rabbits were boosted every 4 to 6 weeks by injecting a total of 1 ml of whole, killed H. capsulatum yeast-phase cells subcutaneously at four dorsal sites.…”

Antibodies to a cell surface histone-like protein protect against Histoplasma capsulatum

“…Exposure to Hc is known to induce an Ab response, and the IgG fraction contains complement-fixing and precipitating Ab's (10). Passive immunization with immune serum has not been shown to mediate protection (11), B cell-deficient mice are not particularly susceptible to infection (12), and high titers of serumspecific Ab to Hc do not correlate with immunity (10). Consequently, the consensus in the field is that humoral immunity has little or no role in host defense.…”

Monoclonal Antibodies to Heat Shock Protein 60 Alter the Pathogenesis ofHistoplasma capsulatum

“…Consistent with the conflicting results of previous experiments with polyclonal sera for fungal infections such as cryptococcosis (8,9,29), administration of polyclonal serum from mice immune to H. capsulatum var. capsulatum did not protect naïve mice from histoplasmosis (39). Interestingly, in vivo experiments with specific monoclonal antibodies (MAbs) to the capsular polysaccharide of the fungus Cryptococcus neoformans have revealed the existence of protective, nonprotective, and disease-enhancing MAbs, suggesting that the divergent results obtained with polyclonal preparations may be a result of the relative proportions of protective and nonprotective antibodies in immune sera (9,16).…”