The capsular polysaccharides of Cryptococcus neoformans activate normal CD4(+) T cells in a dominant Th2 pattern.
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-alpha and IFN-gamma. 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.
Almeida
G M
GM
Programa de Imunobiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Andrade
R M
RM
Bento
C A
CA
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D023201:CD40 Ligand / Q000502:physiology; D002448:Cell Adhesion; D002478:Cells, Cultured; D003455:Cryptococcus neoformans / Q000276:immunology* / Q000472:pathogenicity; D016207:Cytokines / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011134:Polysaccharides / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D016207:Cytokines; D011134:Polysaccharides; D023201:CD40 Ligand