T cell functions in granulocyte/macrophage colony-stimulating factor deficient mice

Immunological functions were analyzed in mice lacking granulocyte/macrophage colony-stimulating factor (GM-CSF), The response of splenic T cells to alloantigens, anti-mouse CD3 mAb, interleukin 2 (IL-2), or concanavalin A was comparable in GM-CSF +/+ and GM-CSF -/-mice, To investigate the responses of CD8(+) and CD4(+) T cells against exogenous antigens, mice were immunized with ovalbumin peptide or with keyhole limpet hemocyanin (KLH), Cytotoxic CD8(+) T cells with specificity for ovalbumin peptide could not be induced in GM-CSF -/-mice, After immunization with KLH, there was a delay in IgG generation, particularly IgG2a, in GM-CSF -/-mice, Purified CD4(+) T cells from GM-CSF -/-mice immunized with KLH showed impaired proliferative responses and produced low amounts of interferon-gamma (IFN-gamma) and IL-4 when KLH-pulsed B cells or spleen cells were used as antigen presenting cells (APC),When enriched dendritic cells (DC) were used as APC, CD4(+) T cells from GM-CSF -/-mice proliferated as well as those from GM-CSF +/+ mice and produced high amounts of IFN-gamma and IL-4. To analyze the rescue effect of DC on CD4(+) T cells, supernatants from (i) CD4(+) T cells cultured with KLH-pulsed DC or (ii) DC cultured with recombinant GM-CSF were transferred to cultures of CD4(+) T cells and KLH-pulsed spleen cells from GM-CSF -/-mice, Supernatants from both DC sources contained a factor or factors that restored proliferative responses and IFN-gamma production of CD4(+) T cells from GM-CSF -/-mice.