Journal article
NK-Dependent Increases in CCL22 Secretion Selectively Recruits Regulatory T Cells to the Tumor Microenvironment
The Journal of immunology (1950), Vol.182(5), pp.2753-2765
03/01/2009
DOI: 10.4049/jimmunol.0801124
PMCID: PMC3337694
PMID: 19234170
Abstract
Tumor-induced immune suppression involves the accumulation of immune-suppressive infiltrates in the microenvironment. This study demonstrates increased numbers of CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) in the lungs of C57BL/6 mice hearing it metastatic Lewis lung carcinoma (LLC) variant. These Tregs suppressed the proliferation of endogenous CD4(+)CD25(-) cells and expressed higher levels of the chemokine receptor CCR4 than other types of T cells. LLC-bearing lungs secreted elevated levels of the CCR4-associated chemokine CCL22 compared with normal lungs. However, CCL22 was not secreted by LLC or normal epithelial controls, suggesting that CCL22 is secreted fly a nonepithelial component of the microenvironment. Migration assays revealed that medium conditioned by LLC-bearing lungs selectively recruited Tregs at higher frequencies than did medium conditioned by normal lungs. Neutralization or CCL22 significantly reduced this selective recruitment toward both conditioned media. A series of immunomagnetic isolations, FACS, and flow cytometric analyses were used to isolate different cellular fractions from both normal and LLC-bearing lungs. When isolated, only the NK-containing fractions secreted CCL22, and the same fraction isolated from LLC-bearing lungs secreted higher levels. Depletion of INK cells from both normal and LLC-bearing lung tissue significantly reduced CCL22 secretion, suggesting that a large portion of secreted CCL22 is NK cell dependent. Flow cytometric analysis of the lung NK compartments revealed no significant increase in NK cell numbers across LLC-bearing lung tissue as a whole as compared with normal tissue. However, immunofluorescent staining revealed an increased frequency of NK cells at the tumor periphery that were closely associated with the elevated FoxP3(+) infiltrate. The Journal of Immunology, 2009, 182: 2753-2765.
Details
- Title: Subtitle
- NK-Dependent Increases in CCL22 Secretion Selectively Recruits Regulatory T Cells to the Tumor Microenvironment
- Creators
- Adam W. Mailloux - Medical University of South CarolinaM. Rita I. Young - Med Univ S Carolina, Dept Otolaryngol, Charleston, SC 29403 USA
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.182(5), pp.2753-2765
- DOI
- 10.4049/jimmunol.0801124
- PMID
- 19234170
- PMCID
- PMC3337694
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Publisher
- Amer Assoc Immunologists
- Number of pages
- 13
- Grant note
- CA8566; R01 CA097813; CA97813; R01 CA128837; R01 CA085266; R01 CA085266-06; R01 CA128837-05 / NCI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) R01CA085266 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 03/01/2009
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984297316502771
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