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The Capsular Polysaccharides of Cryptococcus neoformans Activate Normal CD4⁺ T Cells in a Dominant Th2 Pattern¹

Geisy M. Almeida^*, Regis M. Andrade^* and Cleonice A. M. Bento^2,

^* Programa de Imunobiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; and Instituto de Microbiologia e Parasitologia, Universidade do Rio de Janeiro, Rio de Janeiro, Brazil

Capsular components of Cryptococcus neoformans induce several deleterious effects on T cells. However, it is unknown how the capsular components act on these lymphocytes. The present study characterized cellular and molecular events involved in immunoregulation of splenic CD4⁺ T cells by C. neoformans capsular polysaccharides (CPSs). The results showed that CPSs induce proliferation of normal splenic CD4⁺ T cells, but not of normal CD8⁺ T or B lymphocytes. Such proliferation depended on physical contact between CPSs and viable splenic adherent cells (SAC) and CD40 ligand-induced intracellular signal transduction. The absence of lymphoproliferation after fixation of SAC with paraformaldehyde has discarded the hypothesis of a superantigen-like activation. The evaluation of a cytokine pattern produced by the responding CD4⁺ T lymphocytes revealed that CPSs induce a dominant Th2 pattern, with high levels of IL-4 and IL-10 production and undetectable inflammatory cytokines, such as TNF- and IFN-. Blockade of CD40 ligand by relevant mAb down-regulated the CPS-induced anti-inflammatory cytokine production and abolished the enhancement of fungus growth in cocultures of SAC and CD4⁺ T lymphocytes. Our findings suggest that CPSs induce proliferation and differentiation of normal CD4⁺ T cells into a Th2 phenotype, which could favor parasite growth and thus important deleterious effects to the host.

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