CANDIDA-ALBICANS INDUCES SELECTIVE EXPANSION OF HUMAN T-LYMPHOCYTES EXPRESSING THE T-CELL RECEPTOR VARIABLE REGION V-BETA-5.1

Candida albicans is a common pathogen which can present major problems as an opportunistic skin pathogen in patients with immunodeficiency. The exact nature of the T cell responses to C. albicans is poorly unde rstood. The purpose of this study was to determine whether C. albicans could stimulate the selective expansion of T lymphocytes expressing p articular V beta gene segments. Human T lymphocytes stimulated in vitr o with an extract of C, albicans were analyzed for T cell receptor V b eta gene expression by using a quantitative PCR technique. We found th at stimulation of peripheral blood mononuclear cells (PBMC) produced a selective increase in the expression of V beta 5.1 and 5.2 gene trans cripts. Using cytofluorographic analysis with available anti-V beta mo noclonal antibodies, we verified that there was a significant selectiv e expansion (P = 0.035) of V beta 5.1 positive T lymphocytes in PBMC f rom six subjects stimulated in vitro with C. albicans. PCR analysis of V beta 5.1 expansion in 10 subjects showed increases in V beta 5.1 ge ne transcripts in 7/10 subjects. More importantly, analysis of the T c ell infiltrate 48 h after intradermal injections with C, albicans also showed significant expression of V beta 5.1 in the infiltrates, along with the infiltration of V beta 8.1 + T cells. The selective expansio n of V beta 5.1 bearing T lymphocytes in PBMC stimulated with C. albic ans and in skin test reactions to C. albicans suggests that a restrict ed population of T cells react to C. albicans. Furthermore, our presen t data raise the provocative possibility that one or more antigens in C. albicans can act as a superantigen, producing selective expansion o f a population of T lymphocytes bearing a particular V beta specificit y.