T-CELL FUNCTIONS IN GRANULOCYTE MACROPHAGE COLONY-STIMULATING FACTOR DEFICIENT MICE/

Immunological functions were analyzed in mice lacking granulocyte/macr ophage colony-stimulating factor (GM-CSF), The response of splenic T c ells to alloantigens, anti-mouse CD3 mAb, interleukin 2 (IL-2), or con canavalin A was comparable in GM-CSF +/+ and GM-CSF -/-mice, To invest igate the responses of CD8(+) and CD4(+) T cells against exogenous ant igens, mice were immunized with ovalbumin peptide or with keyhole limp et hemocyanin (KLH), Cytotoxic CD8(+) T cells with specificity for ova lbumin peptide could not be induced in GM-CSF -/-mice, After immunizat ion with KLH, there was a delay in IgG generation, particularly IgG2a, in GM-CSF -/-mice, Purified CD4(+) T cells from GM-CSF -/-mice immuni zed with KLH showed impaired proliferative responses and produced low amounts of interferon-gamma (IFN-gamma) and IL-4 when KLH-pulsed B cel ls or spleen cells were used as antigen presenting cells (APC),When en riched dendritic cells (DC) were used as APC, CD4(+) T cells from GM-C SF -/-mice proliferated as well as those from GM-CSF +/+ mice and prod uced 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 t ransferred to cultures of CD4(+) T cells and KLH-pulsed spleen cells f rom GM-CSF -/-mice, Supernatants from both DC sources contained a fact or or factors that restored proliferative responses and IFN-gamma prod uction of CD4(+) T cells from GM-CSF -/-mice.