Differential requirements for CTL generation by novel immunostimulants: APC tropism, use of the TAP-independent processing pathway, and dependency on CD80/CD86 costimulation
Journal
Vaccine
Journal Volume
21
Journal Issue
25-26
Pages
3775-3788
Date Issued
2003
Author(s)
Sheikh N.A.
Attard G.S.
Van Rooijen N.
Rajananthanan P.
Hariharan K.
YA-WUN YANG
Morrow W.J.W.
Abstract
A major drawback of subunit vaccines is their inability to generate cytolytic T lymphocytes (CTL), a deficit attributed to segregation of the class I and class II antigen-processing pathways. We sought to understand processes involved in CTL induction by three proprietary adjuvants: Tomatine, PROVAX?, and a synthesized glycolipid (Glc-N-(8/16), Glycolipid). We used in vivo models to investigate antigen uptake, macrophage involvement, TAP-independent processing, and costimulatory molecule dependencies. Glycolipid required splenic and lymph node macrophages, whereas Tomatine generated CTL independently of either macrophage population. In contrast, PROVAX? showed partial macrophage requirements. Immunized TAP knockout mice revealed that ovalbumin (OVA)-Tomatine and OVA-PROVAX?, but not OVA-Glycolipid, generate class I-peptide complexes. All three immunostimulants also elicited CD86-dependent TH1 cytokine responses. ? 2003 Elsevier Science Ltd. All rights reserved.
Subjects
Adjuvant; Costimulation; Tomatine
SDGs
Other Subjects
B7 antigen; CD86 antigen; cytokine; glycolipid; immunological adjuvant; ovalbumin; provax; tomatine; unclassified drug; animal cell; animal experiment; animal tissue; antigen presentation; antigen presenting cell; article; cell function; cell subpopulation; cellular immunity; complex formation; controlled study; cytotoxic T lymphocyte; female; immunostimulation; knockout mouse; lymph node cell; lymphocytopoiesis; macrophage; major histocompatibility complex; mouse; nonhuman; priority journal; spleen; Th1 cell
Type
journal article