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In situ differentiation of CD8?? ? cells from CD4 T cells in peripheral lymphoid tissues.

ABSTRACT: Mutually exclusive cell fate determination of CD4 helper or CD8 killer T cells occurs in the thymus. These T-cell subsets are not believed to redirect other lineages. Here we showed that retinoic acid and transforming growth factor-?1 promoted the differentiation of CD8?? T cells from CD4 T cells in a Runx3-dependent manner. These cells were inferred to belong to immunoregulatory populations because subpopulations of CD8??+TCR?? T cells are known to suppress activated T cells, and mice with Runx3(-/-) T cells showed defects during recovery from experimental allergic encephalomyelitis. Our results demonstrate that CD4 T cells play fundamental roles in controlling immune reactions through promotion and attenuation. We accordingly anticipate that clarifying the mechanisms underlying this process will provide insights leading to autoimmune and immunodeficiency disease therapies.

SUBMITTER: Nambu Y

PROVIDER: S-EPMC3435563 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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In situ differentiation of CD8αα Τ cells from CD4 T cells in peripheral lymphoid tissues.

Nambu Yukiko Y Hayashi Tatsunari T Jang Kyoung-Jin KJ Aoki Koji K Mano Hiroto H Nakano Keiko K Osato Motomi M Takahashi Katsu K Itoh Katsuhiko K Teramukai Satoshi S Komori Toshihisa T Fujita Jun J Ito Yoshiaki Y Shimizu Akira A Sugai Manabu M

Scientific reports 20120907

Mutually exclusive cell fate determination of CD4 helper or CD8 killer T cells occurs in the thymus. These T-cell subsets are not believed to redirect other lineages. Here we showed that retinoic acid and transforming growth factor-β1 promoted the differentiation of CD8αα T cells from CD4 T cells in a Runx3-dependent manner. These cells were inferred to belong to immunoregulatory populations because subpopulations of CD8αα+TCRαβ T cells are known to suppress activated T cells, and mice with Runx ...[more]

PMID: 22962636

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Project description:BackgroundStudies assessing immune parameters typically utilize human PBMCs or murine splenocytes to generate data that is interpreted as representative of immune status. Using splenocytes, we have shown memory CD4-T cells that expand following systemic immunostimulatory therapies undergo rapid IFNg-mediated activation induced cell death (AICD) resulting in a net loss of total CD4-T cells which correlates with elevated PD-1 expression. This is in contrast to CD8-T cells which expand with minimal PD-1 upregulation and apoptosis. In this study we expand upon our previous work by evaluating CD4 and CD8-T cell phenotype and distribution in peripheral organs which are more representative of immune responses occurring at metastatic sites following immunotherapy.MethodsPhenotypic assessment of T cells in both lymphoid (spleen and LN) as well as peripheral organs (liver and lungs) in control and immunotherapy treated mice was performed to survey the impact of location on memory phenotype and activation marker status. Peripheral blood from patients undergoing systemic high dose IL-2 was also assessed for expression of PD-1 and memory phenotype.ResultsHere we reveal that, similar to what occurs in the spleen and lymph nodes, CD4-T cell numbers decreased while CD8-T cells expanded at these peripheral sites. In contrast to having differential expression of PD-1 as occurs in the spleen, both CD4 and CD8-T cells had significantly elevated levels of PD-1 in both the liver and lungs. Further analysis correlated PD-1 expression to CD62Llow (T effector/effector memory,TE/EM) expression which are more prevalent in CD4-T cells in general as well as CD8-T cells in peripheral organs. Similar elevated PD-1 expression on TE/EM cells was observed in patients undergoing systemic high-dose IL-2 therapy.ConclusionsThese data highlight PD-1 expressing and/or TE/EM subsets of T cells in circulation as more representative of cells at immune sites and underscore the importance of valuation both in lymphoid as well as target organs when making determinations about immune status.Trial registrationClinicalTrials.gov NCT01416831. Registered August 12, 2011.

Dataset Information

In situ differentiation of CD8?? ? cells from CD4 T cells in peripheral lymphoid tissues.

Publications

In situ differentiation of CD8αα Τ cells from CD4 T cells in peripheral lymphoid tissues.

Similar Datasets

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