Specific regulation of the immune system

is the ultimate goal for the establishment of therapies against diseases associated with inappropriate immune responses such as autoimmune disorders, chronic viral infections and tumours. Previous reports described the mechanisms of immunological impairments in such diseases,[1-4] and impairment of cellular immune responses is considered to be critical for establishing continuous viral infection[3] or tumour progression.[4] Hence, improvement of antigen-specific cellular immune responses will be essential for establishing immune therapies against these diseases as well as humoral or innate immune responses.[5, 6] DNA Damage inhibitor It is well known that cellular and humoral immune responses are regulated through a complicated cascade.[7] Among the elements of that cascade, the T helper (Th) 1/2 cell balance is considered essential to regulate the cellular/humoral immune response.[8, 9] In addition, regulatory T (Treg) cells

are also critical for immune regulation.[10] Treg cells have unique characteristics represented by a lack of response to various antigens and the ability to induce Th cells to enter antigen-specific anergy,[10, 11] and human Treg cells exhibit their inhibitory activity through various pathways.[12] Recently, it has been clarified that Treg cells consist of various subsets[13] including selleck inhibitor naturally occurring Treg (Tregnat) cells that differentiate in the thymus and exhibit inhibitory ability in a cell contact-dependent manner,[14] and adaptive Treg (Tregadapt) cells that differentiate from naive CD4+ T cells under the influence of Tregnat cells[15, 16] and exhibit inhibitory activity in a humoral element-dependent

manner.[17, 18] Although Treg cells were first identified as regulators of autoreactive T cells, Treg cells also induce Palbociclib immune responses against exogenous antigens such as acute or chronic infectious viruses[19, 20] or other endogenous antigens such as tumours.[21, 22] The Treg cells can down-modulate antigen-specific Th1 activity in the later phase of viral infections, which in turn switches the dominant immune response from cellular to humoral.[23] In contrast, over-activation of Treg cells would be the principal reason for the impaired cellular immune response in persistent viral infection, such as with hepatitis C virus (HCV).[24] Hence, regulation of Treg cells may improve impaired cellular immune responses against many endogenous and exogenous antigens. Ribavirin (RBV), a purine nucleotide analogue used as an antiviral reagent,[25] is well known for its contribution to HCV elimination in combination with interferon (IFN).[26] Among the putative mechanisms for the enhancement of viral elimination by RBV, it is notable that RBV polarizes the Th cell balance into Th1 cell dominance.