Enhancement of the human T cell response to culture filtrate fractions of Mycobacterium tuberculosis by microspheres

An improved method of assessment of the human immune response against Mycob acterium tuberculosis antigens will assist the development of new vaccines or diagnostic reagents. In this study, we have analyzed human T cell respon ses to culture filtrate fractions (CFF) of actively replicating M. tubercul osis strain H37Rv using peripheral blood mononuclear cells from healthy PPD skin test positive and negative individuals. Adsorption of CFF onto polyst yrene microspheres, that were approximately the size of the M. tuberculosis (bead-adsorbed antigens, BAA) significantly enhanced IFN-gamma production compared to soluble antigens (SA) in PPD skin test positive individuals in an antigen-specific manner. Further, BAA induced activation of both CD4(+) and CD8(+) T cell subsets. However, CD4(+) responses in general were higher and their antigenic repertoire was wider than the CD8(+) responses. By con trast, CD8(+) responses were strongest to the lower molecular weight BAA. W hen CFF were chemically coupled to carboxyl modified microspheres (bead-cou pled antigens, BCA), induction of IFN-gamma was similar to BAA. Enhancement of T cell responses to particulate M. tuberculosis antigens may prove usef ul in vaccine design strategies. (C) 2000 Elsevier Science B.V. All rights reserved.