Enhancement of CTL Response Induced by a Viral Peptide Using Cationized BSA,a Th1-Stimulating Adjuvant

Abstract

We have recently shown that it is possible to activate cytotoxic T cells (CTL) in vivo with HSV-1 glycoprotein B H-2K^b-restricted peptide (gB peptide) independent of CD4⁺ T cell help. Here we report that the gB peptide-specific CTL response is significantly enhanced when mice are immunized with a mixture of gB peptide and cationized BSA (cBSA). The latter molecule is a positively charged form of the native BSA molecule that stimulates CD4⁺ T cells to produce cytokines characteristic of Th1 cells. The cBSA-enhanced CTL response required the presence of CD4⁺ T cells, but it did not require stimulation in vitro by antigen or exogenous cytokines. gB peptide/cBSA-activated LN cells transcribed IL-2 and IFN-γ, but only IL-2 was essential for CTL development. Our data demonstrate that while activation of CTL may occur in the absence of CD4⁺ cells, cytokines produced by CD4⁺ Th1 cells provide stimulatory signals during CTL maturation. Thus, cotreatment with a substance that activates Th1 CD4⁺ cells may be useful for achieving maximal CTL responsiveness.