Induction of skewed Th1/Th2 T-cell differentiation via subcutaneous immunization with Freund's adjuvant.
CD4+ T cells differentiate into at least two distinct subsets, Th1 and Th2, that are characterized by their cytokine-producing profiles. In this study, we attempted to delineate whether and how CD4+ T-cell responses could be skewed in one direction or another. BALB/c mice were immunized with chicken ovalbumin (OVA) emulsified with either incomplete or complete Freund's adjuvant (IFA or CFA). When lymph node cells were assessed on day 7, antigen specific proliferation was similarly observed both in the mice immunized with IFA and CFA. In contrast, on day 28 there was a less significant response in the mice primed with IFA than in those primed with CFA. ELISA analyses revealed more Th1 predominant cytokine production by T cells immunized with OVA+CFA rather than in IFA, which resulted in balanced IFN-gamma and IL-4 production. Flow cytometric analyses of intracellular cytokines confirmed that T cells from mice primed with CFA produced Th1 cytokines more predominantly. When lymph node dendritic cells (DC) were compared for their co-stimulatory molecule expression, priming with CFA and IFA similarly upregulated CD80 and CD86 expression by lymph node DC, and no significant differences were observed in CD40, 54, 80 and 86 expression between the DC harvested from IFA and CFA immunized mice. In addition, both priming with IFA and CFA similarly induced IL-12 production by DC. Thus, although the reason(s) for the preferential induction of a Th1/Th2 response remains unknown, these results indicate that a relatively Th1/Th2 skewed response is differentially induced by different types of adjuvants, and induction of a Th1 skewed response may be responsible for long lasting cellular immunity.
Shibaki
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Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Katz
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D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D005620:Freund's Adjuvant / Q000008:administration & dosage / Q000145:classification / Q000276:immunology*; D007114:Immunization / Q000379:methods*; D007279:Injections, Subcutaneous; D018664:Interleukin-12 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D018417:Th1 Cells / Q000166:cytology* / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology
D018664:Interleukin-12; D005620:Freund's Adjuvant