Thymocyte emigration is mediated by active movement away from stroma-derived factors

Poznansky, Mark C.; Olszak, Ivona T.; Evans, Richard H.; Wang, Zhengyu; Foxall, Russell B.; Olson, Douglas P.; Weibrecht, Kathryn; Luster, Andrew D.; Scadden, David T.

doi:10.1172/jci13853

Cited by 76 publications

(108 citation statements)

References 28 publications

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“…The basal levels of SDF-1 in plasma have been found to be at ϳ0.6 ng/ml (47), whereas local SDF-1 concentrations in tissues could be high and in the range of ng/ml to g/ml (48,49). In vitro, SDF-1 attracts blood T cells optimally at around 50 -100 ng/ml (50).…”

Section: Cd45ro Memory Cd4 T Cells Is More Sensitive Tomentioning

confidence: 99%

A Dichotomy in Cortical Actin and Chemotactic Actin Activity between Human Memory and Naive T Cells Contributes to Their Differential Susceptibility to HIV-1 Infection

Wang

Guo

et al. 2012

Journal of Biological Chemistry

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Human memory and naive CD4 T cells can mainly be identified by the reciprocal expression of the CD45RO or CD45RA isoforms. In HIV-1 infection, blood CD45RO memory CD4 T cells are preferentially infected and serve as a major viral reservoir. The molecular mechanism dictating this differential susceptibility to HIV-1 remains largely obscure. Here, we report that the different susceptibility of memory and naive T cells to HIV is not determined by restriction factors such as Apobec3G or BST2. However, we observed a phenotypic distinction between human CD45RO and CD45RA resting CD4 T cells in their cortical actin density and actin dynamics. CD45RO CD4 T cells possess a higher cortical actin density and can be distinguished as CD45RO+Actinhigh. In contrast, CD45RA T cells are phenotypically CD45RA+Actinlow. In addition, the cortical actin in CD45RO memory CD4 T cells is more dynamic and can respond to low dosages of chemotactic induction by SDF-1, whereas that of naive cells cannot, despite a similar level of the chemokine receptor CXCR4 present on both cells. We further demonstrate that this difference in the cortical actin contributes to their differential susceptibility to HIV-1; resting memory but not naive T cells are highly responsive to HIV-mediated actin dynamics that promote higher levels of viral entry and early DNA synthesis in resting memory CD4 T cells. Furthermore, transient induction of actin dynamics in resting naive T cells rescues HIV latent infection following CD3/CD28 stimulation. These results suggest a key role of chemotactic actin activity in facilitating HIV-1 latent infection of these T cell subsets.

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Section: Cd45ro Memory Cd4 T Cells Is More Sensitive Tomentioning

confidence: 99%

A Dichotomy in Cortical Actin and Chemotactic Actin Activity between Human Memory and Naive T Cells Contributes to Their Differential Susceptibility to HIV-1 Infection

Wang

Guo

et al. 2012

Journal of Biological Chemistry

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“…Activated K-ras causes inflammation in lung tumors H Ji et al sufficiently elevated, the gradient may repel cells that are normally recruited by a given chemokine, a property known as chemofugetaxis (Poznansky et al, 2002). To determine which chemokines were involved in the recruitment of these inflammatory cells into the lungs of the CC10-Cre/LSL-K-ras G12D mice, we measured the levels of several C-C and C-X-C chemokines, molecules known for their monocyte and neutrophil chemotactic properties, respectively, in BAL fluid from these mice (Walz et al, 1991;Baggiolini et al, 1994;Baggiolini et al, 1995) (Figure 4).…”

Section: Activated K-ras Causes Inflammation In Lung Tumorsmentioning

confidence: 99%

K-ras activation generates an inflammatory response in lung tumors

et al. 2005

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Activating mutations in K-ras are one of the most common genetic alterations in human lung cancer. To dissect the role of K-ras activation in bronchial epithelial cells during lung tumorigenesis, we created a model of lung adenocarcinoma by generating a conditional mutant mouse with both Clara cell secretory protein (CC10)-Cre recombinase and the Lox-Stop-Lox K-ras G12D alleles. The activation of K-ras mutant allele in CC10 positive cells resulted in a progressive phenotype characterized by cellular atypia, adenoma and ultimately adenocarcinoma. Surprisingly, K-ras activation in the bronchiolar epithelium is associated with a robust inflammatory response characterized by an abundant infiltration of alveolar macrophages and neutrophils. These mice displayed early mortality in the setting of this pulmonary inflammatory response with a median survival of 8 weeks. Bronchoalveolar lavage fluid from these mutant mice contained the MIP-2, KC, MCP-1 and LIX chemokines that increased significantly with age. Cell lines derived from these tumors directly produced MIP-2, LIX and KC. This model demonstrates that K-ras activation in the lung induces the elaboration of inflammatory chemokines and provides an excellent means to further study the complex interactions between inflammatory cells, chemokines and tumor progression.

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“…1-3 SDF-1 is constitutively expressed by stromal, endothelial, dendritic, and other cells. [4][5][6] It stimulates the motility of hematopoietic cells, lymphocytes, and monocytes, 7,8 thymocytes, 9 and mediates leukocyte adhesion to the vascular endothelium. 10 SDF-1 also influences the development of microglia, astrocytes, and neurons.…”

Section: Introductionmentioning

confidence: 99%

Haplotype analysis of the SDF-1 (CXCL12) gene in a longitudinal HIV-1/AIDS cohort study

et al. 2005

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The stromal-derived factor-1 (SDF-1) chemokine gene encodes the only natural ligand for CXCR4, the coreceptor for the pathogenic X4 HIV-1 strains. A single-nucleotide polymorphism (SNP) in the 3 0 untranslated region (SDF1-3 0 A ¼ rs1801157) of SDF-1 was reported to be protective against infection and progression in some, but not other, epidemiological studies. To identify additional alleles that may influence HIV-1 infection and progression to AIDS, nine SNPs (including rs1801157) spanning 20.2 kb in and around the SDF-1 gene were genotyped in over 3000 African American (AA) and European American (EA) participants enrolled in five longitudinal HIV-1/AIDS natural cohort studies. Six or five haplotypes were present at frequencies greater than 5% in AA or EA, respectively. Six of the nine SNPs occur on only one common haplotype (45%), while the remaining three SNPs were found on multiple haplotypes, suggesting a complex history of recombination. Among EA, rs754618 was associated with an increased risk of infection (OR ¼ 1.50, P ¼ 0.03), while rs1801157 ( ¼ SDF1-3 0 A) was associated with protection against infection (OR ¼ 0.63, P ¼ 0.01). In the MACS cohort, rs1801157 was associated with AIDS-87 (RH ¼ 0.31, P ¼ 0.02) and with death (RH ¼ 0.18, P ¼ 0.02). Significant associations to a single disease outcome were found for two SNPs and one haplotype in AA.

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Thymocyte emigration is mediated by active movement away from stroma-derived factors

Cited by 76 publications

References 28 publications

A Dichotomy in Cortical Actin and Chemotactic Actin Activity between Human Memory and Naive T Cells Contributes to Their Differential Susceptibility to HIV-1 Infection

A Dichotomy in Cortical Actin and Chemotactic Actin Activity between Human Memory and Naive T Cells Contributes to Their Differential Susceptibility to HIV-1 Infection

K-ras activation generates an inflammatory response in lung tumors

Haplotype analysis of the SDF-1 (CXCL12) gene in a longitudinal HIV-1/AIDS cohort study

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