Dendritic Cells in the Induction of Protective and Nonprotective Anticryptococcal Cell-Mediated Immune Responses

• Published in: The Journal of immunology (1950) 2000-07, Vol.165 (1), p.158-167
• Main Authors: Bauman, Sean K, Nichols, Kasie L, Murphy, Juneann W
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Animals; Antigens, CD; Antigens, Fungal - administration & dosage; Antigens, Fungal - immunology; Apoptosis - immunology; B7-1 Antigen - biosynthesis; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes - immunology; CD40 Antigens - biosynthesis; Cell Movement - immunology; Cryptococcosis - immunology; Cryptococcosis - mortality; Cryptococcosis - prevention & control; Cryptococcus neoformans; Cryptococcus neoformans - immunology; Culture Media; Dendritic Cells - cytology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Female; Flow Cytometry; Freund's Adjuvant - administration & dosage; Freund's Adjuvant - immunology; Fungal Vaccines - administration & dosage; Fungal Vaccines - immunology; Hematopoietic Stem Cells - immunology; Hematopoietic Stem Cells - metabolism; Histocompatibility Antigens Class II - biosynthesis; Hypersensitivity, Delayed - immunology; Hypersensitivity, Delayed - prevention & control; Immunity, Cellular; Immunophenotyping; Kinetics; Langerhans Cells - cytology; Langerhans Cells - immunology; Langerhans Cells - metabolism; Lectins, C-Type; Leukocyte Count; Leukocytes - immunology; Lymph Nodes - cytology; Lymph Nodes - immunology; Lymph Nodes - metabolism; Lymphocyte Activation - immunology; Lymphocyte Subsets - cytology; Lymphocyte Subsets - immunology; Lymphocyte Subsets - metabolism; Membrane Glycoproteins - analysis; Mice; Mice, Inbred CBA; Minor Histocompatibility Antigens; Receptors, Cell Surface - analysis; Survival Analysis; T-Lymphocytes - immunology; Vaccines, Inactivated - administration & dosage; Vaccines, Inactivated - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.165.1.158

Dendritic cells (DC) can be divided into three subsets, Langerhans cells, myeloid DC (MDC), and lymphoid DC (LDC), based upon phenotypic and functional differences. We hypothesized that different DC subsets are associated with the development of protective vs nonprotective cell-mediated immune (CMI) responses against the fungal pathogen, Cryptococcus neoformans. To test this, mice were immunized with protective and/or nonprotective immunogens, and DC subsets in draining lymph nodes were assessed by flow cytometry. The protective immunogen (cryptococcal culture filtrate Ag-CFA), in contrast to the nonprotective immunogen (heat-killed cryptococci-CFA), the nonprotective immunogen mixed with the protective immunogen (cryptococcal culture filtrate Ag + heat-killed cryptococci-CFA), or controls, stimulated significant increases in total leukocytes, Langerhans cells, MDC, LDC, and activated CD4+ T cells in draining lymph nodes. The protective immune response resulted in significantly increased levels of anticryptococcal delayed-type hypersensitivity reactivity and activated CD4+ T cells at the delayed-type hypersensitivity reaction site. Draining lymph node LDC:MDC ratios induced by the protective immunogen were significantly lower than the ratios induced by either immunization in which the nonprotective immunogen was present. In contrast, mice given the nonprotective immunogen had LDC:MDC ratios similar to those of naive mice. Our data indicate that lymph node Langerhans cells and MDC are APC needed for induction of the protective response. The predominance of LDC in mice undergoing nonprotective responses suggests that lymph node LDC, like splenic LDC, are negative regulators of CMI responses. In addition to showing DC subsets associated with functional differences, our data suggest that the LDC:MDC balance, which can be modulated by the Ag, determines whether protective or nonprotective anticryptococcal CMI responses develop.