[Allergies: determinants of T2 lymphocyte polarization and desensitization mechanisms]

Distinguishing two populations amongst T lymphocytes, namely Th1 and Th2, has enabled a better understanding of the pathophysiology of inflammatory diseases most notably immunoallergic disorders. These two populations, initially described in mice, are defined by the profile of cytokines which they produce. Th1 lymphocytes secrete amongst others IL-2 and IFN-gamma and the action exercised by these cytokines are involved in cellular reactions. Th2 lymphocytes are involved in humoral responses and immediate hypersensitivity secreting IL-4 and IL-5. In man the distinction between the two populations is more subtle than in the mouse, in particular for the same cell there is a possibility to pass from one type of cytokine to another. Thus the importance of factors which influence the orientation towards Th1 or Th2 type amongst the T lymphocytes. What are these factors? Can one use these to change the response to achieve a therapeutic goal? These are the questions that we propose to touch on in this analysis broaching the induction of the Th2 response. Certain responses are linked to the individual and concern their heredity. Others are the cells themselves which are involved in antigen presentation, the presenting cell and the HLA molecules, peptide antigen and T cell receptor. Again there are others which influence the presentation without being directly involved: these are the cytokines already present in the biological milieu and engaged co-receptors. All these factors act in concert, perhaps with others which are not yet known and account for the complexity of the response. Desensitisation is a treatment whose efficacy is recognised in certain precise indications. During the course of treatment, there is a diminution of IgE to the benefit of IgG and a diminution of the eosinophil count induced by specific provocation. These effects may be related to a decrease in the production of IL-4 and IL-5 respectively, which has been found in several recent studies. Desensitisation also shows that in spite of its complexity, one can reorientate towards a Th1 response based on spontaneous Th2 response. In this respect desensitisation constitutes a human model for the study of orientation of the Th2 immune response. In the future better understanding of the mechanisms of the allergic reaction will enable new treatments to be developed based on the use of antigenic peptides or using cytokines and inhibitors of cytokines.