RESUMO
Regulated glycosylation controls T cell processes, including activation, differentiation and homing by creating or masking ligands for endogenous lectins. Here we show that stimuli promoting T helper type 1 (TH1), TH2 or interleukin 17-producing T helper (TH-17) differentiation can differentially regulate the glycosylation pattern of T helper cells and modulate their susceptibility to galectin-1, a glycan-binding protein with anti-inflammatory activity. Although TH1- and TH-17-differentiated cells expressed the repertoire of cell surface glycans critical for galectin-1-induced cell death, TH2 cells were protected from galectin-1 through differential sialylation of cell surface glycoproteins. Consistent with those findings, galectin-1-deficient mice developed greater TH1 and TH-17 responses and enhanced susceptibility to autoimmune neuroinflammation. Our findings identify a molecular link among differential glycosylation of T helper cells, susceptibility to cell death and termination of the inflammatory response.
Assuntos
Apoptose/imunologia , Galectina 1/imunologia , Inflamação/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Auxiliares-Indutores/metabolismo , Transferência Adotiva , Animais , Diferenciação Celular/imunologia , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/metabolismo , Citometria de Fluxo , Galectina 1/genética , Galectina 1/metabolismo , Glicosilação , Humanos , Immunoblotting , Marcação In Situ das Extremidades Cortadas , Inflamação/metabolismo , Interleucina-17/metabolismo , Glicoproteínas de Membrana/imunologia , Glicoproteínas de Membrana/metabolismo , Camundongos , Polissacarídeos/imunologia , Polissacarídeos/metabolismo , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/patologia , Linfócitos T Auxiliares-Indutores/citologia , Linfócitos T Auxiliares-Indutores/patologia , Células Th1/citologia , Células Th1/metabolismo , Células Th1/patologia , Células Th2/citologia , Células Th2/metabolismo , Células Th2/patologiaRESUMO
We examined specific immunoglobulin G1 (IgG1) and IgG3 responses to Plasmodium falciparum schizont and Schistosoma mansoni egg and worm antigens in individuals from Kenya, Uganda, and the Sudan who had been exposed to malaria and schistosomiasis. A strong correlation between malaria- and schistosome-specific IgG3 responses was observed. This association appears to result from the presence of cross-reactive components of the 2 parasites that bind IgG3 antibodies, rather than to be mediated by immunological cross-regulation or specific regulatory mechanisms induced by either parasite. Cross-reactivity of IgG3 antibodies was confirmed in a Brazilian cohort of individuals living in an area where schistosomiasis is endemic but no malaria occurs and in a Pakistani cohort from an area where malaria is endemic but no schistosomiasis occurs. An IgG3 interaction with antigens from both parasites was observed in individuals from both cohorts, but not in uninfected European control subjects. The immunological and biological implications of this observation require further exploration.