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Human γδ T cells in diverse tissues exhibit site-specific maturation dynamics across the life span

ABSTRACT: Early in ontogeny, gd T cells emerge from the thymus and directly seed peripheral tissues for in situ immunity, though their function in human tissues is not clear. Through analysis of gd T cells in mucosal and lymphoid tissues across the human lifespan, we reveal age- and site-specific differentiation states, functions, and dynamics. Pediatric tissues uniquely contain newly generated gd T cells with diverse repertoires, exhibiting tissue repair and effector functions. In adult tissues, gd T cells persist in lower frequencies, exhibiting highly expanded repertoires and cytolytic profiles. Over childhood, gd T cells convert to adult-like differentiation profiles in mucosal sites, revealing that gd T cells provide diverse recognition and functions for numerous antigenic challenges during early life but persist as terminally differentiated, innate-like cells thereafter.

ORGANISM(S): Homo sapiens

PROVIDER: GSE240858 | GEO | 2024/04/01

REPOSITORIES: GEO

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Project description:gd T cells recognize unprocessed or non-peptide antigens, respond rapidly to infection, and localize to mucosal surfaces. We have hypothesized that the innate functions of gd T cells may be more similar to those of cells of the myeloid lineage than to other T cells. To begin to test this assumption, we have analyzed the direct response of cultured human and peripheral blood bovine gd T cells to pathogen associated molecular patterns (PAMPs) in the absence of APCs using microarray, real time RT-PCR, proteome array, and chemotaxis assays. Our results indicate that purified gd T cells respond directly to PAMPs by increasing expression of chemokine and activation related genes. The response was distinct from that to known gd T cell antigens and different from the response of myeloid cells to PAMPs. In addition, we have analyzed the expression of a variety of PAMP receptors in gd T cells. Freshly purified bovine gd T cells responded more robustly to PAMPs than did cultured human cells and expressed measurable mRNA encoding a variety of PAMP receptors. Our results suggest that rapid response to PAMPs through the expression of PAMP receptors may be another innate role of gd T cells. Experiment Overall Design: Sorted cells from 4 human gd T cell cultures were treated with either PBS or phLPS for 4 hours, RNA was extracted with TRIzolÂ® Reagent (Invitrogen Life Technologies) according to the manufacturerâs instructions, pooled and used to probe Affymetrix GenechipÂ® Human Genome U133A 2.0 Arrays (Cat. # 900471 Affymetrix, Santa Clara, CA) that represent 14,500 human genes. cDNA amplification and synthesis of biotin-labeled cRNA was performed with the Alternative One-cycle target labeling protocol with 10 micrograms total RNA as described in the GeneChipÂ® Expression Analysis Technical Manual (March 2004). Hybridization was performed with 10 micrograms biotin labeled cRNA. Washing and staining was performed in the GeneChipÂ® Fluidics Station 450 using the Midi_euk2v3 protocol. Chip scans were performed on the Affymetrix GeneChipÂ® Scanner 3000. GeneChipÂ® Operating Software (GCOS v.1.1, Affymetrix) was used for data collection.

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Human γδ T cells in diverse tissues exhibit site-specific maturation dynamics across the life span

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