Dendritic cells in the induction of protective and nonprotective anticryptococcal cell-mediated immune responses

Dendritic cells (DC) can be divided into three subsets, Langerhans cells, m yeloid 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 thi s, mice were immunized with protective and/or nonprotective inmunogens, and DC subsets in draining lymph nodes were assessed by flow cytometry. The pr otective immunogen (cryptococcal culture filtrate Ag-CFA), in contrast to t he nonprotective immunogen (heat-killed cryptococci-CFA), the nonprotective immunogen mixed with the protective immunogen (cryptococcal culture filtra te Ag + heat-killed cryptococci-CFA), or controls, stimulated significant i ncreases in total leukocytes, Langerhans cells, MDC, LDC, and activated CD4 (+) T cells in draining lymph nodes. The protective immune response resulte d in significantly increased levels of anticryptococcal delayed-type hypers ensitivity reactivity and activated CD4(+) T cells at the delayed-type hype rsensitivity reaction site. Draining lymph node LDC:MDC ratios induced by t he protective immunogen were significantly lower than the ratios induced by either immunization in which the nonprotective immunogen was present. In c ontrast, 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 predom inance of LDC in mice undergoing nonprotective responses suggests that lymp h 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, de termines whether protective or nonprotective anticryptococcal CMI responses develop.