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T cells cooperate with passive antibody to modify Cryptococcus neoformans infection in mice
1Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Abstract:
Cryptococcus neoformans is an encapsulated fungus that is a major cause of meningitis in patients with AIDS. In immunocompetent mice, administration of IgG1 mAb protects against cryptococcal infection, whereas administration of IgG3 is not protective and can accelerate the infection. In beige mice with impaired natural killer cell function, the effects of IgG1 and IgG3 are similar to those observed in immunocompetent mice, suggesting that natural killer cells are not crucial for antibody-mediated modulation of cryptococcal infection. In mice lacking CD4+ T cells, IgG1 is not protective and IgG3 accelerates infection, indicating that CD4+ T cells are required for antibody-mediated protection. In mice lacking CD8+ T cells, both IgG1 and IgG3 antibodies prolong survival, indicating that acceleration of the disease process by IgG3 involves CD8+ T cells. Both IgG1-mediated protection and IgG3-mediated acceleration of infection require interferon gamma. These results reveal a functional dependence of passively administered antibody on cellular immunity in cryptococcal infection in mice and have implications for antibody-based therapies in humans in the setting of CD4+ lymphopenia.
Insights
Antibody therapy for cryptococcal meningitis in AIDS patients needs T cell support. IgG1 antibodies protect against fungal infection, but only when CD4+ T cells are present.
Area of Science:
- Immunology
- Infectious Diseases
- Mycology
Background:
- Cryptococcus neoformans causes meningitis, particularly in AIDS patients.
- Antibody therapy effectiveness varies, with IgG1 protective and IgG3 accelerating infection in mice.
Purpose of the Study:
- To investigate the role of cellular immunity in antibody-mediated protection against Cryptococcus neoformans infection.
- To determine the influence of CD4+ T cells, CD8+ T cells, and natural killer cells on antibody efficacy.
Main Methods:
- Administration of IgG1 and IgG3 monoclonal antibodies (mAbs) to immunocompetent and immunodeficient mouse models.
- Evaluation of survival rates and disease progression in mice lacking specific immune cell populations (CD4+, CD8+, beige mice).
- Assessment of interferon gamma's role in antibody-mediated effects.
Main Results:
- CD4+ T cells are essential for IgG1-mediated protection against cryptococcal infection.
- CD8+ T cells are involved in the acceleration of infection by IgG3 antibodies.
- Natural killer cells do not play a crucial role in antibody-mediated outcomes.
- Interferon gamma is required for both IgG1 protection and IgG3-mediated acceleration.
Conclusions:
- Passive antibody administration efficacy in cryptococcal infection is functionally dependent on cellular immunity in mice.
- Findings have implications for developing antibody-based therapies for cryptococcal meningitis in human patients with CD4+ lymphopenia.