Differential clonal expansion of CD4 and CD8 T cells in response to 4-1BB ligation: contribution of 4-1BB during inflammatory responses.
Cell surface proteins of the tumor necrosis factor (TNF) family of receptors have been intimately involved in inducing T cell death. A feature of these family members that is less well studied is their ability to rescue T cells from apoptosis. One such member is 4-1BB; an activation induced surface receptor on CD4 and CD8 T cells. This study demonstrates that the costimulatory effects of 4-1BB, which was found to enhance clonal expansion, required cross-linking of the receptor. The survival of the activated CD8 T cells following expansion was not associated with an increase in Bcl-2 expression. Provided that 4-1BB signaling was present, the amplification of activated CD8 T cell growth in vivo was independent of CD28 ligation. In vivo clonal expansion of activated CD4 T cells, however, was not as responsive to 4-1BB cross-linking. Moreover, 4-1BB-induced expansion was comparable to that mediated by LPS which can incite multiple costimulatory signals. Furthermore, LPS-mediated growth and survival of superantigen (SAg) stimulated T cells appeared to be partially dependent on interactions between 4-1BB and 4-1BB ligand (4-1BBL).
Takahashi
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Department of Microbiology, 220 Nash Hall, Oregon State University, Corvallis, OR 97331, USA.
Mittler
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RS
Vella
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D053330:4-1BB Ligand; D000818:Animals; D015703:Antigens, CD; D018106:CD28 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D002454:Cell Differentiation; D002999:Clone Cells; D005260:Female; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D018089:Superantigens / Q000378:metabolism / Q000494:pharmacology; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D053330:4-1BB Ligand; D015703:Antigens, CD; D018106:CD28 Antigens; D008070:Lipopolysaccharides; D019253:Proto-Oncogene Proteins c-bcl-2; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; D018089:Superantigens; C505715:Tnfrsf9 protein, mouse; C505975:Tnfsf9 protein, mouse; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha