Immunomodulation of T-cell responses with Vibrio cholerae O135 capsular polysaccharide and its protein conjugate, novel cholera vaccine study models

Abstract

We studied T-cell immune responses to surface capsular polysaccharide (CPS) of Vibrio cholerae O135 and its protein conjugate. CPS and CPS-bovine serum albumin (BSA) activation and presentation are characterized with induced alterations in expression and upregulation of membrane antigens CD25, CD11b, CD16/32, MHCII and CD45 on blood- and spleen-derived T cells. Expression of the early activation marker CD25 revealed efficient CPS-BSA conjugate activation especially of CD4+CD3+ and CD8+ CD3+ cells. Specific CPS-BSA-induced CD25+ T-cell subsets in blood were observed after the first application, i.e. a 4.2-fold increase of CD4+CD25+ and 7.6-fold increase of CD8+CD25+ vs. preimmune levels was determined. The upregulation of surface antigens MHCII and CD45 involved in antigen presentation and cell activation of CD3+ cells and their significant reciprocal correlation (R2 = 0.92) observed only with CPS-BSA conjugate suggested efficient T-cell dependency and presentation. The pattern of accelerated T-cell activation and engagement of T cells as antigen-presenting cells throughout CPS-BSA immunization contrary to CPS alone was also confirmed in CD4+/CD8+/CD3+ splenic cells. The results revealed different T-cell antigen presentation and activation following administration of CPS and CPS-BSA conjugates, as supported also by evaluation of CD45, MHCII and CD25 expression on CD19+ B cells. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.