RESUMEN
Interleukin 17 (IL-17)-producing CD4(+) helper T cells (T(H)-17 cells) share a developmental relationship with Foxp3(+) regulatory T cells (T(reg) cells). Here we show that a T(H)-17 population differentiates in the thymus in a manner influenced by recognition of self antigen and by the cytokines IL-6 and transforming growth factor-beta (TGF-beta). Like previously described T(H)-17 cells, the T(H)-17 cells that developed in the thymus expressed the transcription factor RORgamma t and the IL-23 receptor. These cells also expressed alpha(4)beta(1) integrins and the chemokine receptor CCR6 and were recruited to the lung, gut and liver. In the liver, these cells secreted IL-22 in response to self antigen and mediated host protection during inflammation. Thus, T(H)-17 cells, like T(reg) cells, can be selected by self antigens in the thymus.
Asunto(s)
Autoantígenos/inmunología , Linfocitos T CD4-Positivos/inmunología , Diferenciación Celular/inmunología , Interleucina-17/metabolismo , Subgrupos de Linfocitos T/inmunología , Timo/citología , Animales , Linfocitos T CD4-Positivos/citología , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Inflamación/inmunología , Integrina alfa4beta1/biosíntesis , Interleucina-23/biosíntesis , Interleucina-6/inmunología , Interleucina-6/metabolismo , Interleucinas/metabolismo , Ratones , Ratones Transgénicos , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares , Reacción en Cadena de la Polimerasa , Receptores CCR6/biosíntesis , Receptores de Ácido Retinoico/biosíntesis , Receptores de Hormona Tiroidea/biosíntesis , Subgrupos de Linfocitos T/citología , Timo/inmunología , Factor de Crecimiento Transformador beta/inmunología , Factor de Crecimiento Transformador beta/metabolismo , Interleucina-22RESUMEN
CD4+ T(H)17 cells display a featured role in barrier immunity. This effector population of T cells is important for clearance of microorganisms but can also promote autoimmunity at barrier sites. Recent work has indicated that these effector cells share a pathway with CD4+ regulatory T cells (T(R) cells) that also have a critical function in barrier protection and immune regulation. The development and function of T(H)17 cells, and their relationship with T(R) cells are discussed.
Asunto(s)
Linfocitos T CD4-Positivos/metabolismo , Tracto Gastrointestinal/inmunología , Interleucina-17/inmunología , Interleucina-17/metabolismo , Pulmón/inmunología , Piel/inmunología , Animales , Enfermedades Autoinmunes/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/patología , Diferenciación Celular , Tracto Gastrointestinal/patología , Humanos , Inmunidad Celular , Inmunidad Mucosa , Infecciones/inmunología , Interleucina-17/química , Pulmón/patología , Transducción de Señal , Piel/patología , Linfocitos T Reguladores/inmunología , Activación TranscripcionalRESUMEN
The role of specialized follicular helper T (T(FH)) cells in the germinal center has become well recognized, but it is less clear how effector T cells govern the extrafollicular response, the dominant pathway of high-affinity, isotype-switched autoantibody production in the MRL/MpJ-Fas(lpr) (MRL(lpr)) mouse model of lupus. MRL(lpr) mice lacking the Icos gene have impaired extrafollicular differentiation of immunoglobulin (Ig) G(+) plasma cells accompanied by defects in CXC chemokine receptor (CXCR) 4 expression, interleukin (IL) 21 secretion, and B cell helper function in CD4 T cells. These phenotypes reflect the selective loss of a population of T cells marked by down-regulation of P-selectin glycoprotein ligand 1 (PSGL-1; also known as CD162). PSGL-1(lo) T cells from MRL(lpr) mice express CXCR4, localize to extrafollicular sites, and uniquely mediate IgG production through IL-21 and CD40L. In other autoimmune strains, PSGL-1(lo) T cells are also abundant but may exhibit either a follicular or extrafollicular phenotype. Our findings define an anatomically distinct extrafollicular population of cells that regulates plasma cell differentiation in chronic autoimmunity, indicating that specialized humoral effector T cells akin to T(FH) cells can occur outside the follicle.