In:
Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 3292-3292
Kurzfassung:
Abstract 3292 Previous studies have demonstrated that many T cell subsets possess NK-like features, including the CD56+ and KIR+ populations. Collectively, these studies showed that these NK-like T cells are predominantly αβ+ CD8+ with memory phenotype and could recognize HLA-E associated viral peptides after expansion upon TCR engagement. However, their clonality, transcriptome, regulation, specificity, and memory response in human have not been fully elucidated. We hypothesize that these NK-like T cells are phenotypically and functionally distinct from conventional T and NK cells and they play unique roles in virus and cancer control. Herein, we extensively characterized the CD56+ T cells and the KIR+ T subset by analysis of TREC, TCRVβ spectrum, telomere length, surface biomarkers, genome-wide transcriptome, multi-analyte cytokine profiling, cancer cell susceptibility, tetramer staining, and real-time response to CMV reactivation in stem cell transplant recipients. In contrast to CD56– T cells, CD56+ T cells are limited in TREC, TCRVβ, telomere length, cytokine secretion, transcription of metabolic genes stx6, nnt, galnt2, hvcn1, tyms, rpa1 tmf1, ecop, and tspan3, and are mostly KIR+, CD8+, DNAM1+, NKG2D+, CD44+, NKp46– and CD25–. Compared to KIR– CD56+ T cells, KIR+ CD56+ T cells are even more limited in TREC, TCRVβ, telomere length, and cytokine secretion, but have elevated transcription of NK cytotoxicity-related genes arrb1, ppp3cc, and lamc3, higher degranulation after activation by IL-2/IL-15 and CD3/CD28 antibodies, better killing of cancer cells after cytokine priming, and are mostly KIR2DL2/3+, NKG2D+, NKp46+, CD16+, NKG2C+, CD57+, and 2B4+. Importantly during CMV reactivation after stem cell transplantation, the percentage of KIR+ CD56+ T cells in the patient's blood increased dramatically and was significantly higher (p=0.0021) than in those without viral reactivation. Ex vivo, KIR+ CD56+ T cells demonstrate CMVpp65 tetramer staining, memory response to CMV peptides, and potent lysis of CMVpp65-pulsed target cells dependent on both KIR and TCR specificity. Furthermore, we identified for the first time that KIR– CD56+ T cells are Rorc+ IL-13-secretor. In conclusion, both CD56+ and KIR+ NK-like T-cell subsets are unique in biological and clinical properties and have distinct roles in cancer and infection control. Disclosures: No relevant conflicts of interest to declare.
Materialart:
Online-Ressource
ISSN:
0006-4971
,
1528-0020
DOI:
10.1182/blood.V120.21.3292.3292
Sprache:
Englisch
Verlag:
American Society of Hematology
Publikationsdatum:
2012
ZDB Id:
1468538-3
ZDB Id:
80069-7
