Abstract
Conventional and nonconventional T cell development occur in the thymus. Nonconventional thymocytes that bear characteristics typically associated with innate immune cells are termed innate-like lymphocytes (ILLs). Mice harboring a tyrosine to phenylalanine mutation in the adaptor protein Src homology 2 domain-containing leukocyte protein of 76 kDa at residue 145 (Y145F mice) develop an expanded population of CD8(+)CD122(+)CD44(+) ILLs, typified by expression of the T-box transcription factor eomesodermin. Y145F mice also have an expanded population of γδ T cells that produce copious amounts of IL-4 via a mechanism that is dependent on the BTB-ZF transcription factor promyelocytic leukemia zinc finger. Using mice with T cell-specific deletion of Eomes, we demonstrate that this transcription factor is required for CD8(+) ILL development in Y145F as well as wild-type mice. Moreover, we show that promyelocytic leukemia zinc finger and IL-4 are also required for the generation of this ILL population. Taken together, these data shed light on the cell-intrinsic and cell-extrinsic factors that drive CD8(+) ILL differentiation.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / immunology*
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Amino Acid Substitution
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Animals
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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Cells, Cultured
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Flow Cytometry
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Interferon-gamma / immunology
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Interferon-gamma / metabolism
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Interleukin-4 / immunology
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Interleukin-4 / metabolism
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Kruppel-Like Transcription Factors / genetics
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Kruppel-Like Transcription Factors / immunology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mutation
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Phosphoproteins / genetics
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Phosphoproteins / immunology*
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Promyelocytic Leukemia Zinc Finger Protein
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T-Box Domain Proteins / genetics
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T-Box Domain Proteins / immunology*
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Thymus Gland / cytology
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Thymus Gland / immunology
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Thymus Gland / metabolism
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Zinc Fingers / genetics
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Zinc Fingers / immunology
Substances
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Adaptor Proteins, Signal Transducing
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Eomes protein, mouse
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Kruppel-Like Transcription Factors
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Phosphoproteins
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Promyelocytic Leukemia Zinc Finger Protein
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SLP-76 signal Transducing adaptor proteins
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T-Box Domain Proteins
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Zbtb16 protein, mouse
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Interleukin-4
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Interferon-gamma