MODIFICATION OF CYTOKINE PATTERNS IN SUBJECTS BEARING THE HLA-B8,DR3 PHENOTYPE - IMPLICATIONS FOR AUTOIMMUNITY

The factors influencing the pathogenesis of autoimmune disease are not fully known, but the host genotype undoubtedly plays a role in determ ining the outcome of these diseases. The role of the host's major hist ocompatibility complex (MHC) genotype in the regulation of susceptibil ity to autoimmune diseases has keen extensively studied in different p opulations, and certain HLA (the human MHC) alleles and haplotypes hav e been reported to be associated with several autoimmune diseases. In particular, the association with genes from the HLA-B8,DR3 haplotype h as been reported by different research groups. This haplotype is assoc iated in all Caucasian populations with a wide variety of diseases wit h autoimmune features, and in healthy subjects it is associated with a number of immune system dysfunctions. Mainly, peripheral blood mononu clear cells from HLA-B8,DR3-positive and -negative individuals differ in their ability to produce interleukin (IL)-2, IL-5, IL-12 and interf eron-gamma upon stimulation with the mitogen phytohaemoagglutinin (PHA ), while producing similar amounts of IL-4, IL-6 and IL-10. Furthermor e, in HLA-B8,DR3-positive subjects tumor necrosis factor alpha secreti on is increased both with and without PHA stimulation. Accurate contro l of the functional repertoire of an immune response is a critical par ameter in the response to infections as well as in immunopathology. MH C control of the class of the immune response at the level of cytokine production is a sophisticated way In which this occurs. This control might be involved in adaptive immune responses to infections as well a s in immunopathology.