Immunological adjuvants promote activated T cell survival via induction of Bcl-3.
Injection of soluble protein antigen into animals causes abortive proliferation of the responding T cells. Immunological adjuvants boost T cell responses at least in part by increasing the survival of activated T cells during and after the initial proliferative phase of their clonal expansion. To understand how adjuvants promote T cell survival, we used gene microarrays to analyze gene expression in T cells activated either with antigen alone or in the presence of two different adjuvants. Among the genes whose expression was increased by both adjuvants was the IkappaB family member Bcl-3. Retroviral infection experiments showed that expression of Bcl-3 increased survival of activated T cells in vitro and in vivo. Adjuvants may therefore improve survival of activated T cells via induction of Bcl-3.
Mitchell
T C
TC
Howard Hughes Medical Institute, University of Colorado Health Sciences Center, Denver, CO 80206, USA.
Hildeman
D
D
Kedl
R M
RM
Teague
T K
TK
Schaefer
B C
BC
White
J
J
Zhu
Y
Y
Kappler
J
J
Marrack
P
P
D000276:Adjuvants, Immunologic; D000818:Animals; D000081242:B-Cell Lymphoma 3 Protein; D016923:Cell Death; D005260:Female; D020869:Gene Expression Profiling; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014157:Transcription Factors; D014616:Vaccinia virus / Q000276:immunology
D000276:Adjuvants, Immunologic; D000081242:B-Cell Lymphoma 3 Protein; C000631345:Bcl3 protein, mouse; D008070:Lipopolysaccharides; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors