Immunopathology and oligoclonal T cell expansions. Observations in immunodeficiency, infections, allergy and autoimmune diseases

ABSTRACT The immune system is usually seen as a collection of independent (specific) lymphocyte clones. Randomly generated and activated at random, these lymphocytes follow only their individual, clonal history. Thus, in traditional descriptions, immunological activity is neither systemic nor historical and is never “physiological”. However, recent descriptions show an abundant “auto”-reactivity in healthy organisms, an evidence of internal connectivity. The two major sources of immunogenic contacts, namely, dietary proteins and products of the autochthonous microbiota fail to induce progressive “secondary-type” clonal expansions (or “memory”). Natural IgM may arise in “antigen-free” organisms as they do in conventionally raised animals; actually, clonal receptors of both T and B lymphocytes are formed in antigen-free intracellular environments and are not driven by antigen exposure. Early in ontogenesis natural immunoglobulins are organized in characteristic patterns of reactivity which are robustly stable throughout healthy living;