Regulatory T cells essential to prevent the loss of self-tolerance in murine models of erythrocyte-specific autoantibody responses.

The spontaneous appearance of anti-erythrocyte autoantibodies resulting in autoimmune hemolytic anemia described in NZB mice more than 40 years ago provided a model for the study of mechanisms behind the loss of self-tolerance. We developed an in vitro model of this anti-MRBC response in which CD8(+) suppressor T cells were shown to be a controlling element. CD8(+) T cells from young NZB mice co-cultured with spleen cells from old, actively autoimmune NZB mice suppressed the anti-MRBC responses of the old mice.

Transient inhibition of Th1-type cytokine production by CD4 T cells in hepatitis B core antigen immunized mice is mediated by regulatory T cells.

The non-cytopathic hepatitis B virus (HBV) can induce chronic infections characterized by weak and limited T cell responses against the virus. The factors contributing to the failure to clear HBV and subsequent development of chronic HBV infections are not clearly understood, but a strong interferon-gamma (IFN-gamma) response by CD4+ T cells against the nucleocapsid hepatitis B core antigen (HBcAg) of the virus appears to be important for viral clearance. The present study documents depressed numbers of CD4+ T cells secreting IFN-gamma and interleukin-2 (IL-2) in enzyme-linked immunospot assay (ELISPOT) assays restimulated for 24 hr with antigen following both primary and secondary immunizations of mice with recombinant hepatitis B core antigen (rHBcAg).

Different response requirements for IFNgamma production in ELISPOT assays by CD4+ T cells from mice early and late after immunization.

Antigen specific immune responses that occur early after antigen exposure differ from those that are present late in the response. The present study focused on detecting changes in production of IFNgamma by CD4+ T cells over time during chronic antigen exposure. (C3HxCB17)F1 mice were primed with recombinant hepatitis B core antigen (rHBcAg) in incomplete Freund's adjuvant to allow persistent antigen exposure.