Antigen-Driven Effector CD8 T Cell Function Regulated by T-bet

Type 1 immunity relies on the differentiation of two major subsets of T lymphocytes, the CD4+T helper (Th) cell and the CD8+cytotoxic T cell, that direct inflammatory and cytotoxic responses essential for the destruction of intracellular and extracellular pathogens. In contrast to CD4 cells, little...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 100; no. 26; pp. 15818 - 15823
Main Authors Sullivan, Brandon M., Juedes, Amy, Szabo, Susanne J., von Herrath, Matthias, Glimcher, Laurie H.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 23.12.2003
National Acad Sciences
Subjects
Animals
Antibodies
Antigen presenting cells
Biological Sciences
CD8-Positive T-Lymphocytes - immunology
Cell lines
Crosses, Genetic
Cultured cells
Cytokines
Deoxyribonucleic acid
DNA
Immunology
Infections
Lymphatic system
Lymphocyte Activation
Lymphocytic Choriomeningitis - immunology
Lymphocytic choriomeningitis virus
Mice
Mice, Knockout
Spleen cells
Splenocytes
T cell antigen receptors
T lymphocytes
T-Box Domain Proteins
T-Lymphocytes, Cytotoxic - immunology
T-Lymphocytes, Helper-Inducer - immunology
Transcription Factors - deficiency
Transcription Factors - genetics
Transcription Factors - immunology
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Summary:Type 1 immunity relies on the differentiation of two major subsets of T lymphocytes, the CD4+T helper (Th) cell and the CD8+cytotoxic T cell, that direct inflammatory and cytotoxic responses essential for the destruction of intracellular and extracellular pathogens. In contrast to CD4 cells, little is known about transcription factors that control the transition from the CD8$na{\ddot \imath} ve$to effector cell stage. Here, we report that the transcription factor T-bet, known to regulate Th cell differentiation, also controls the generation of the CD8+cytotoxic effector cell. Antigen-driven generation of effector CD8+cells was impaired in OT-I T cell receptor transgenic mice lacking T-bet, resulting in diminished cytotoxicity and a marked shift in cytokine secretion profiles. Furthermore, mice lacking T-bet responded poorly to infection with lymphocytic choriomeningitis virus. T-bet is a key player in the generation of type 1 immunity, in both Th and T cytotoxic cells.
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Contributed by Laurie H. Glimcher, October 27, 2003
Abbreviations: CTL, cytotoxic T lymphocyte; Th, T helper; TCR, T cell receptor; LCMV, lymphocytic choriomeningitis virus; PE, phycoerythrin; FACS, fluorescence-activated cell sorting; PMA, phorbol 12-myristate 13-acetate; CFSE, carboxyfluorescein diacetatesuccinimidyl ester; APC, antigen-presenting cell.
To whom correspondence should be addressed. E-mail: lglimche@hsph.harvard.edu.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2636938100