Effect of superantigens on human thymocytes: Selective proliferation of Vβ2+ cells in response to toxic shock syndrome toxin-1 and their deletion upon secondary stimulation

Abstract

The effects of toxic shock syndrome toxin-1 (TSST-1) on human thymocytes and their CD4/CD8-defined subsets have been analyzed. Postnatal thymocyte cell suspensions were cultured with 5 ng/ml TSST-1 for different time intervals. A strong cell proliferation of CD3+/TCR+ cells, characterized by selective expansion of cells expressing TCR Vβ2, occurred. In these cultured thymocytes, Vβ2+ cells were detected in all subsets including CD4-CD8+ cells. CD4-CD8+ thymocyte populations (obtained by depletion of CD4+ cells) were further analyzed for their ability to directly respond to TSST-1. An efficient cell proliferation occurred; however, it was completely abrogated upon removal of HLA class II+ cells (representing ∼10% of fresh thymocytes depleted of CD4+ cells). The HLA class II dependency of TSST-1-mediated functions was further documented at the clonal level. Thus, in the presence of TSST-1, CD4-CD8+ Vβ2+ clones efficiently lysed the HLA class II+ Raji target cells but not the corresponding HLA class II- variant RJ 2.2.5. Analysis of the effect of TSST-1-induced secondary stimulation on cultured (Vβ2+-enriched) thymocytes resulted in a selective depletion of Vβ2+ cells due to apoptotic cell death.