ACCESSORY CELL REQUIREMENTS FOR SAPONIN ADJUVANT-INDUCED CLASS-I MHC ANTIGEN-RESTRICTED CYTOTOXIC T-LYMPHOCYTES

The in vivo and in vitro accessory cell requirements of class I major histocompatability complex (MHC) antigen-restricted cytotoxic T-lympho cyte (CTL) responses were determined using cell-depletion experiments coupled with active immunizations using ovalbumin (OVA) as the immunog en and saponin adjuvant (QS-21). To paralyze macrophage activity in vi vo, C57BL/6 mice were treated with particulate silica or carrageenan. In vivo depletion of helper T-lymphocytes was accomplished by treatmen t with GK1.5 rat monoclonal antibody, which is specific for the murine CD4 antigen, and by genetic depletion of class II MHC antigens. Follo wing treatments, the mice were immunized with formulations containing OVA alone or mixed with QS-21 saponin adjuvant, which induces MHC clas s I antigen-restricted CTL responses. In vivo treatment to paralyze ma crophages abrogated these CTL responses but not antigen-specific antib ody or lymphocyte proliferative responses. Depletion of CD4(+) T-lymph ocytes had no effect on CTL responses but significantly reduced prolif eration and antibody responses. In vitro depletion and reconstitution experiments were done to compare the contributions of different antige n-presenting cells (APC), specifically dendritic cells (DC) and macrop hages. Again, the requirement for macrophages was absolute but there w as no indication that DC were involved. These data suggest that antige n processing and presentation functions are critical to the induction of CTL and that they are a function of macrophages but that CD4(+) hel per T-lymphocyte functions are not required. (C) 1994 Academic Press, Inc.