RESUMO
The concept that T cells are subdivided into T helper 1 (Th1) and Th2 subsets was recently extended to suggest that Th1 cells contribute to the pathogenesis of several organ-specific autoimmune diseases, whereas Th2 cells inhibit disease development. Here, Sylvie Trembleau and colleagues examine the role of interleukin 12 (IL-12), a key cytokine guiding the development of Th1 cells, in the induction of autoimmune diseases, and discuss potential immunointervention strategies based on administration of IL-12 antagonists.
Assuntos
Doenças Autoimunes/imunologia , Interleucina-12/fisiologia , Especificidade de Órgãos/imunologia , Células Th1/imunologia , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Artrite/induzido quimicamente , Artrite/imunologia , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/tratamento farmacológico , Colágeno/toxicidade , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/imunologia , Desenho de Fármacos , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/terapia , Feminino , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Imunoterapia Adotiva , Interleucina-12/antagonistas & inibidores , Interleucina-12/toxicidade , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos NOD , Modelos ImunológicosRESUMO
The absolute concentrations of mouse immunoglobulin (Ig) heavy chain isotypes were determined by specific ELISAs in the serum of C57BL/6 (B6) mice doubly homozygous at the nude (nu) and the lymphoproliferation (lpr) locus (B6 nu, lpr mice), and compared with normal B6 nu mice. The distribution and the absolute concentrations of all Ig isotypes were found to be very similar in B6 nu, lpr and B6 nu mice, for both sexes and with similar increases in titers with ageing. Thus, the major part of the severe autoimmunity and hyperglobulinemia characteristic of the lpr syndrome of euthymic B6 lpr mice, including their elevated titers of thymus-independent IgM and IgG3 isotypes, is abrogated by the nude mutation, an effect of which is the lack of thymus differentiation. Though a postulated intrinsic activity of the lpr gene directly on B cell hyperactivity cannot be discarded, its expression would then require the presence of either the thymus or of T cells or of other cells or factors whose expression is also abrogated by the homozygosity at the nude locus.