Functional inactivation of Dermatophagoides spp. (house dust mite) reactive human T-cell clones.
Staphylococcal enterotoxins are able both to stimulate powerful polyclonal proliferative responses and to induce non-responsiveness of T lymphocytes expressing the appropriate T-cell antigen receptor V beta gene products. T-cell clones representative of the human response to house dust mite were identified that express either V beta 3 or V beta 6 gene products. The specificity of the latter was confirmed by serology. Pre-treatment of cloned V beta 3+ T cells with the Staphylococcus aureus enterotoxins B or C1 rendered them non-responsive to immunogenic challenge with their natural ligand, while retaining responsiveness to exogenous IL-2. Similarly, exposure of the V beta 6+ dust mite reactive T cells to the staphylococcal enterotoxin of the appropriate specificity, SEE, induced specific anergy. The development of non-responsiveness was associated with changes in the T-cell phenotypes. Downregulation of the T-cell receptor, Ti-CD3, was paralleled by enhanced expression of both CD2 and the IL-2 receptor, CD25. Differential co-modulation of CD4 and Ti-CD3 suggested that for some T cells CD4 may form part of the specific antigen recognition structure. Toxicity of the staphylococcal enterotoxins may be removed by chemical modification, thus their ability functionally to inactivate subpopulations of T cells expressing antigen-specific receptors with shared characteristics may be of potential value in the regulation of allergic diseases if the diversity of the T-cell repertoire proves to be limited.
O'Hehir
R E
RE
ImmuLogic Pharmaceutical Corporation, Palo Alto, California.
Aguilar
B A
BA
Schmidt
T J
TJ
Gollnick
S O
SO
Lamb
J R
JR
D000818:Animals; D002999:Clone Cells / Q000276:immunology; D004768:Enterotoxins / Q000494:pharmacology; D006801:Humans; D008213:Lymphocyte Activation; D008925:Mites / Q000276:immunology*; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013211:Staphylococcus aureus; D013601:T-Lymphocytes / Q000276:immunology*
D004768:Enterotoxins; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta