Effect of superantigens on human thymocytes: Selective proliferation of V(beta)2(+) cells in response to toxic shock syndrome toxin-1 and their deletion upon secondary stimulation

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 V(beta)2, occurred. In these cultured thymocytes, V(beta)2(+) 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 similar to 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(+) V(beta)2(+) 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 (V(beta)2(+)-enriched) thymocytes resulted in a selective depletion of V(beta)2(+) cells due to apoptotic cell death.