Les sous-populations de lymphocytes Th1 et Th2: caractérisation, rôle physiologique et régulation

Abstract

The immune system encountering an antigen can develop cell- and/or antibody-mediated immune responses. Accessory cells uptake the antigen, degrade it into peptides and present them in association with major histocompatibility complex (MHC) molecules to T lymphocytes. The interactions between T-cell receptor and antigen-MHC complex and between various adhesion or costimulatory molecules lead to the activation of CD4⁺ helper T cells or of CD8⁺ cytotoxic T cells. Activated CD4⁺ T cells modulate other immune responses by directly interacting with macrophages, B lymphocytes and CD8⁺ T cells or by soluble mediators, such as cytokines.

Among murine CD4⁺ T cells, two main subsets, Th1 and Th2, were identified based on the pattern of secreted cytokines and on the preferential help for some Ig isotypes. Th1 and Th2 subsets are involved in different immune functions and reciprocally regulate each other. A similar dichotomy was also described for CD8⁺ T cells. The differential activation of the Th1 or Th2 subset is a crucial parameter implicated in the protective or pathologic outcome of many infectious diseases caused by parasites, bacteria and viruses, of allergic disorders and of autoimmune diseases. Many factors were demonstrated to be involved in the regulation of Th1 and Th2 cell subsets, such as the dose and form of antigen, the route of immunization, the adjuvants employed, the genetic background of the animals, the costimulatory molecules and the antigen-presenting cells. Cytokines also exert a critical role in the selective activation of these populations, with IL4 and IL12 being required, respectively, to induce Th2 and Th1 cell activation.