The CD4+ T-cell response to protein immunization is independent of accompanying IFN-gamma-producing CD8+ T cells.

By virtue of their strong bias towards production of interferon-gamma (IFN-gamma), CD8+ T cells have the potential to promote the development of type 1 immune responses. We have previously shown that the CD4+ T-cell response to immunization with the protein antigen keyhole limpet haemocyanin (KLH) has a mixed interleukin-4 (IL-4)/IFN-gamma production profile. Here we show that this immunization regimen also stimulates accumulation in the draining lymph nodes of CD8+ T cells, which preferentially contain IFN-gamma mRNA ex vivo and secrete IFN-gamma protein in vitro. This provides a model to test whether CD8+ cell-derived IFN-gamma participates in the normal control of the immune response to a non-viable exogenous antigen. To investigate regulation of the anti-KLH response by the CD8+ population or IFN-gamma produced by this or other cell types, mice were administered depleting antibodies. Depletion of CD8+ cells had no effect on the frequency of clonogenic KLH-specific CD4+ T cells, the IL-4/IFN-gamma profiles of their progeny, or the isotype profiles of the serum antibody response to KLH. In contrast, IFN-gamma neutralization diminished cell accumulation in the lymph nodes and reduced both the frequency of KLH-specific CD4+ T cells that gave rise to IFN-gamma-producing clones and serum titres of KLH-specific IgG2a and IgG3. Therefore, despite the potential for cross-regulation, the CD4+ T-cell response to this immunogen is independent of the IFN-gamma-skewed CD8+ response.