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 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.
Mingari
M C
MC
Centro Biotecnologie Avanzate, Genova, Italy.
Cambiaggi
A
A
Vitale
C
C
Schiavetti
F
F
Bellomo
R
R
Poggi
A
A
D001427:Bacterial Toxins; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002675:Child, Preschool; D017637:Clonal Deletion / Q000187:drug effects*; D002999:Clone Cells; D003601:Cytotoxicity Tests, Immunologic; D004768:Enterotoxins / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000145:classification / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology
D001427:Bacterial Toxins; D015704:CD4 Antigens; D016827:CD8 Antigens; D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal