We are celebrating this year the hundred years anniversary of allergen-specific immunotherapy. In 1911 Leonard Noon published his seminal work "Prophylactic inoculation against hay fever" describing his attempts to achieve active immunity against "grass pollen toxin" by administering increasing doses of grass pollen extract before the grass pollen season to allergic patients. Although it was unknown at that time that allergy represents an immunological hypersensitivity disease, the treatment was effective and many observations made by Noon remained valid until today. Today allergen-specific immunotherapy is well established as the only allergen-specific and disease-modifying treatment for IgE-mediated allergies and has long-lasting effects. In fact, more than 25% of the population suffer from IgE-mediated allergies which therefore represent a major health burden of our society, particularly because untreated allergy often progresses to severe disabling forms of disease, such as asthma and sometimes kills sensitized people through anaphylaxis."

We are celebrating this year the hundred years anniversary of allergen-specific immunotherapy. In 1911 Leonard Noon published his seminal work "Prophylactic inoculation against hay fever" describing his attempts to achieve active immunity against "grass pollen toxin" by administering increasing doses of grass pollen extract before the grass pollen season to allergic patients. Although it was unknown at that time that allergy represents an immunological hypersensitivity disease, the treatment was effective and many observations made by Noon remained valid until today. Today allergen-specific immunotherapy is well established as the only allergen-specific and disease-modifying treatment for IgE-mediated allergies and has long-lasting effects. In fact, more than 25% of the population suffer from IgE-mediated allergies which therefore represent a major health burden of our society, particularly because untreated allergy often progresses to severe disabling forms of disease, such as asthma and sometimes kills sensitized people through anaphylaxis.

It has been 12 years since the first proposal was made to sub- divide mouse CD4 I T cell clones into Th I and Th2 subsets, based on their differences in cytokine production, and 7 years since the first clear demonstration of a similar dichotomy among human T cell clones. In the ensuing period, it has been realized that inappropriate development of Th I or Th2 responses are important features of many immunological and infectious dis- eases. Perhaps the first group of diseases to be understood in terms of preferential Th subset activation were allergic diseases (see PARRONC'HI et aI. , this volume). Several of the major, co- ordinately regulated, features of allergy, including IgE, eosino- philia and mastocytosis, were found to be stimulated by the T- specific cytokines I L-4 and IL-5 and inhibited by the Th I cyto- kine, IFN-. This suggested that the presence and severity of al- lergic responses reflected the relative numbers of Th I and Th2 cells specific for the offending allergen. Similarly, the very dif- ferent consequences of protective Th I and nonprotective Th2 responses to a number of intracellular pathogens have been re- cognized for some time (see TRINCHIERI and SCOTI, and COFF- MAN et aI. , this volume).