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 V_β2, occurred. In these cultured thymocytes, V_β2⁺ 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⁺ V_β2⁺ 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_β2⁺-enriched) thymocytesresulted in a selective depletion of V_β2⁺ cells due to apoptotic cell death.