Unknown,Transcriptomics,Genomics,Proteomics

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TCR signal strength controls thymic differentiation of discrete proinflammatory Î³Î´T cell subsetsistinct TCR signal strength requirements in the thymus

ABSTRACT: The murine thymus produces discrete Î³Î´ T cell subsets making either IFN-Î³ or IL-17, but the role of the TCR in this developmental process remains controversial. Here we generated a non-transgenic and polyclonal model of reduced TCR expression and signal strength selectively on Î³Î´ T cells. Mice haploinsufficient for both CD3Î³ and CD3Î´ (CD3DH) showed normal Î±Î² thymocyte subsets but specific defects in Î³Î´ T cell development, namely impaired differentiation of IL-17-producing embryonic VÎ³6+ (but not adult VÎ³4+) Î³Î´ T cells and a marked depletion of IFN-Î³-producing CD122+ NK1.1+ (VÎ³1-biased) Î³Î´ T cells throughout life. As result, adult CD3DH mice showed defective peripheral IFN-Î³ responses and were resistant to experimental cerebral malaria. Thus, strong TCR signaling is required within specific developmental windows with distinct VÎ³ usage and differential cytokine production by effector Î³Î´ T cell subsets. We investigated the transcriptional changes associated with reduced TCRÎ³Î´ signaling in the CD3DH model. Transcriptome-wide analysis of FACS-purified CD3DH or WT Î³Î´ thymocytes from E18 or 6-week was carried looking for patterns of gene expression during ontogeny

ORGANISM(S): Mus musculus

SUBMITTER: Ana Grosso

PROVIDER: E-GEOD-71637 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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