Human IL-18 Receptor and ST2L Are Stable and Selective Markers for the Respective Type 1 and Type 2 Circulating Lymphocytes

Chan, Weng Onn; Pejnović, Nada; Lee, Christine A.; Al-Ali, Nadia A.

doi:10.4049/jimmunol.167.3.1238

Cited by 77 publications

(56 citation statements)

References 52 publications

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“…The IL18RAP promoter region lies between IL18R1 and IL18RAP genes both of which are T H 1-specific IL-12-inducible genes (18,38). As expected, IL18Rap and IL-18 receptor 1 mRNA were higher in T H 1 cells (Fig.…”

Section: Preferential Histone Acetylation Of the Ifng Gene In Human Tmentioning

confidence: 59%

Discrete Roles for Histone Acetylation in Human T Helper 1 Cell-specific Gene Expression

Morinobu¹,

Kanno²,

O’Shea

2004

Journal of Biological Chemistry

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To better understand the control of T helper (T H ) 1-expressed genes, we compared and contrasted acetylation and expression for three key genes, IFNG, TBET, and IL18RAP and found them to be distinctly regulated. The TBET and the IFNG genes, but not the IL18RAP gene, showed preferential acetylation of histones H3 and H4 during T H 1 differentiation. Analysis of acetylation of specific histone residues revealed that H3(Lys-9), H4(Lys-8), and H4(Lys-12) were preferentially modified in T H 1 cells, suggesting a possible contribution of acetylation of these residues for induction of these genes. On the other hand, the acetylation of IL18RAP gene occurred both in T H 1 and T H 2 cells with the similar kinetics and on the same residues, demonstrating that selective histone acetylation was not universally the case for all T H 1-expressed genes. Histone H3 acetylation of IFNG and TBET genes occurred with different kinetics, however, and was distinctively regulated by cytokines. Interleukin (IL)-12 and IL-18 enhanced the histone acetylation of the IFNG gene. By contrast, histone acetylation of the TBET gene was markedly suppressed by IL-4, whereas IL-12 and IL-18 had only modest effects suggesting that histone acetylation during T H 1 differentiation is a process that is regulated by various factors at multiple levels. By treating Th2 cells with a histone deacetylase inhibitor, we restored histone acetylation of the IFNG and TBET genes, but it did not fully restore their expression in T H 2 cells, again suggesting that histone acetylation explains one but not all the aspects of T H 1-specific gene expression.

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Section: Preferential Histone Acetylation Of the Ifng Gene In Human Tmentioning

confidence: 59%

Discrete Roles for Histone Acetylation in Human T Helper 1 Cell-specific Gene Expression

Morinobu¹,

Kanno²,

O’Shea

2004

Journal of Biological Chemistry

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“…Th2 cells reportedly express both ␣ and ␤ IFN-␥R chains, but Th1 cells express only IFN-␥R␣ (18,19). Expression of the ST2L molecule is also limited to Th2 cells (20). We found that ϳ7% of skin resident T cells expressed both IFN-␥R␣ and IFN-␥R␤, consistent with a Th2 phenotype, and that a similar percentage expressed the additional Th2 marker ST2L (mean ϭ 7%, range 5-11%, n ϭ 3 donors; Fig.…”

Section: Memory T Cells Can Be Functionally Divided Into Ccr7mentioning

confidence: 76%

The Vast Majority of CLA+ T Cells Are Resident in Normal Skin

Clark

Chong

Mirchandani

et al. 2006

The Journal of Immunology

697

664

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There are T cells within normal, noninflamed skin that most likely conduct immunosurveillance and are implicated in the development of psoriasis. We isolated T cells from normal human skin using both established and novel methods. Skin resident T cells expressed high levels of CLA, CCR4, and CCR6, and a subset expressed CCR8 and CXCR6. Skin T cells had a remarkably diverse TCR repertoire and were mostly Th1 memory effector cells with smaller subsets of central memory, Th2, and functional T regulatory cells. We isolated a surprising number of nonexpanded T cells from normal skin. To validate this finding, we counted T cells in sections of normal skin and determined that there are ∼1 × 106 T cells/cm2 normal skin and an estimated 2 × 1010 T cells in the entire skin surface, nearly twice the number of T cells in the circulation. Moreover, we estimate that 98% of CLA+ effector memory T cells are resident in normal skin under resting conditions. These findings demonstrate that there is a large pool of memory T cells in normal skin that can initiate and perpetuate immune reactions in the absence of T cell recruitment from the blood.

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“…FACS staining of leukocytes isolated from the allergic lung was performed using an Ab specific for the Th2-specific surface marker T1/ST2. This marker is specific and selective for Th2 cells (2,32,33) and enables an estimation of the proportion of Th2 cells to be made. We determined that the proportion of CD4 ϩ T1/ST2 ϩ was not significantly affected by the neutralization of CCL1 in an allergen/sensitization model.…”

Section: Discussionmentioning

confidence: 99%

CC Chemokine Ligand 1 Promotes Recruitment of Eosinophils But Not Th2 Cells During the Development of Allergic Airways Disease

Bishop

Lloyd

2003

The Journal of Immunology

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One of the characteristic features of allergic asthma is recruitment of large numbers of inflammatory cells including eosinophils and Th2 lymphocytes to the lung. This influx of inflammatory cells is thought to be a controlled and coordinated process mediated by chemokines and their receptors. It is thought that distinct, differential expression of chemokine receptors allows selective migration of T cell subtypes in response to the chemokines that bind these receptors. Th2 cells preferentially express CCR8 and migrate selectively to its ligand, CC chemokine ligand (CCL)1. We studied the role of the CCR8 ligand, CCL1, in the specific recruitment of Th2 cells and eosinophils to the lung in a murine model of allergic airway disease. We have demonstrated for the first time that CCL1 is up-regulated in the lung following allergen challenge. Moreover, a neutralizing Ab to CCL1 reduced eosinophil migration to the lung, but had no effect on recruitment of Th2 cells following allergen challenge. In addition, there was no change in airway hyperresponsiveness or levels of Th2 cytokines. In a Th2 cell transfer system of pulmonary inflammation, anti-CCL1 also failed to affect recruitment of Th2 cells to the lung following allergen challenge. Significantly, intratracheal instillation of rCCL1 increased recruitment of eosinophils but not Th2 cells to the lung in allergen-sensitized and -challenged mice. In summary, our results indicate that CCL1 is important for the pulmonary recruitment of eosinophils, rather than allergen-specific Th2 cells, following allergen challenge.

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Human IL-18 Receptor and ST2L Are Stable and Selective Markers for the Respective Type 1 and Type 2 Circulating Lymphocytes

Cited by 77 publications

References 52 publications

Discrete Roles for Histone Acetylation in Human T Helper 1 Cell-specific Gene Expression

Discrete Roles for Histone Acetylation in Human T Helper 1 Cell-specific Gene Expression

The Vast Majority of CLA+ T Cells Are Resident in Normal Skin

CC Chemokine Ligand 1 Promotes Recruitment of Eosinophils But Not Th2 Cells During the Development of Allergic Airways Disease

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