EFFECT OF SUPERANTIGENS ON HUMAN THYMOCYTES - SELECTIVE PROLIFERATIONOF V(BETA)2(-1 AND THEIR DELETION UPON SECONDARY STIMULATION() CELLS IN RESPONSE TO TOXIC SHOCK SYNDROME TOXIN)

The effects of toxic shock syndrome toxin-1 (TSST-1) on human thymocyt es and their CD4/CD8-defined subsets have been analyzed. Postnatal thy mocyte cell suspensions were cultured with 5 ng/ml TSST-1 for differen t 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 detect ed in all subsets including CD4(-)CD8(+) cells. CD4(-)CD8(+) thymocyte populations (obtained by depletion of CD4(+) cells) were further anal yzed for their ability to directly respond to TSST-1. An efficient cel l proliferation occurred; however, it was completely abrogated upon re moval of HLA class II+ cells (representing similar to 10% of fresh thy mocytes 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 efficient ly 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-indu ced secondary stimulation on cultured (V(beta)2(+)-enriched) thymocyte s resulted in a selective depletion of V(beta)2(+) cells due to apopto tic cell death.