Potent Costimulation of Effector T Lymphocytes by Human Collagen Type I

Rao, Wei; Hales, Jonathan M.; Camp, R.D.R.

doi:10.4049/jimmunol.165.9.4935

Cited by 57 publications

(56 citation statements)

References 33 publications

(35 reference statements)

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“…Although the reasons for preferential homing, survival and/or proliferation of CD49b ϩ memory Th cells in the bone marrow are unknown, it may be related to a unique combination of collagen and laminin isoform expression by bone marrow stromal cells (38,39). CD49b in T cells has also been suggested to function as a costimulatory molecule, enhancing TCR-mediated signals (23,40). However, a costimulatory function of CD49b alone could not account for the functional differences between CD49b…”

Section: Discussionmentioning

confidence: 91%

Functional Specialization of Memory Th Cells Revealed by Expression of Integrin CD49b

Kassiotis¹,

Gray

Kiafard

et al. 2006

The Journal of Immunology

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Infection or immunization induces heterogeneous memory T cell subsets, but their origin and protective value against infection are unclear. In this study, we report the functional characterization of two memory Th subsets, defined by expression of integrin CD49b. Stable CD49b expression is induced in up to one-half of all memory Th cells. More importantly, the CD49b− and CD49b+ subsets display distinct helper activities, typified by the production of IL-10 and TNF-α, respectively. Although the inflammatory properties of the CD49b+ subset are protective against intracellular bacterial infection, they are associated with immunopathology in acute viral infection. Modulation of the CD49b-defined memory Th subsets may provide infection type-specific interventions, where either enhancement of the inflammatory response or reduction of immunopathology is essential.

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Section: Discussionmentioning

confidence: 91%

Functional Specialization of Memory Th Cells Revealed by Expression of Integrin CD49b

Kassiotis¹,

Gray

Kiafard

et al. 2006

The Journal of Immunology

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“…In the reconstruct, human melanoma is recapitulated in vitro using a mixture of collagen and fibroblasts (lattices or matrices). Ag-elicited T cells are stimulated by collagen, most likely through the interaction of a2 and b1 integrins on T cells with collagen [8]. Since activated fibroblasts play an important role in the activation of T lymphocytes, they were included in the reconstruct.…”

Section: Discussionmentioning

confidence: 99%

“…CTL MLTC35 (90.0% CD8 + positive; Fig. 1B and Table 3) expressed a2 and b1 integrins (Table 3), which are important for T cell activation by collagen in the reconstruct [7,8]. LFA-1a, ICAM-1, and CD44 expressed by the CTL (Table 3) facilitate interaction of the lymphocytes with fibroblasts in the reconstruct [9].…”

Section: Functional Characteristics Of Ctl Mltc35 In the Reconstructmentioning

confidence: 99%

Migration of cytotoxic T lymphocytes toward melanoma cells in three‐dimensional organotypic culture is dependent on CCL2 and CCR4

et al. 2006

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Studies in experimental animal models have demonstrated that chemokines produced by tumor cells attract chemokine receptor-positive T lymphocytes into the tumor area. However, in cancer patients, the role of chemokines in T lymphocyte trafficking toward human tumor cells is relatively unexplored. In the present study, the migration of a melanoma patient's CTL toward autologous tumor cells has been studied in a novel three-dimensional organotypic melanoma culture. In this model, CTL migrated toward tumor cells, resulting in tumor cell apoptosis. CTL migration was mediated by the CC chemokine receptor (CCR)4 expressed by the CTL and the CC chemokine ligand (CCL)2 secreted by the tumor cells, as evidenced by blockage of CTL migration by CCL2 or antibodies to CCL2 or CCR4. These results were confirmed in a Transwell migration assay in which the CTL actively migrated toward isolated CCL2 and migration was inhibited by anti-CCR4 antibody. These studies, together with previous studies in mice indicating regression of CCL2-transduced tumor cells, suggest that CCL2 may be useful as an immunotherapeutic agent for cancer patients.

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“…In the reconstruct, human melanoma is recapitulated in vitro using a mixture of collagen and fibroblasts (lattices or matrices). Ag-elicited T cells are stimulated by collagen, most likely through the interaction of ␣ 2 (CD49b) and ␤ 1 (CD29) integrins on T cells with collagen (22,23). Because activated fibroblasts play an important role in the activation of T lymphocytes, they were included in the reconstruct.…”

Section: Discussionmentioning

confidence: 99%

“…The cells also express CD95 (FAS), and adhesion and costimulatory molecules (Table II). Expression of ␣ 2 (CD49b) and ␤ 1 (CD29) integrins by T cells (Table II) is important for T cell interaction with collagen in the reconstruct, which results in T cell activation (22,23). LFA-1a (CD11a), ICAM-1 (CD54), and CD44 expressed by the CTL (Table II) facilitate interaction of the lymphocytes with fibroblasts in the reconstruct (24,25).…”

Section: Phenotypic Characteristics Of Ctl793-b and Wm793 Melanoma Cellsmentioning

confidence: 99%

CXC Chemokine Ligand 12 (Stromal Cell-Derived Factor 1α) and CXCR4-Dependent Migration of CTLs toward Melanoma Cells in Organotypic Culture

Zhang

Somasundaram

Berencsi

et al. 2005

The Journal of Immunology

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Studies in experimental animal models have demonstrated that chemokines produced by tumor cells attract chemokine receptor-positive T lymphocytes into the tumor area, which may lead to tumor growth inhibition in vitro and in vivo. However, in cancer patients, the role of chemokines in T lymphocyte trafficking toward human tumor cells is relatively unexplored. In the present study, the role of chemokines and their receptors in the migration of a melanoma patient’s CTL toward autologous tumor cells has been studied in a novel organotypic melanoma culture, consisting of a bottom layer of collagen type I with embedded fibroblasts followed successively by a tumor cell layer, collagen/fibroblast separating layer, and, finally, a top layer of collagen with embedded fibroblasts and T cells. In this model, CTL migrated from the top layer through the separating layer toward tumor cells, resulting in tumor cell apoptosis. CTL migration was mediated by chemokine receptor CXCR4 expressed by the CTL and CXCL12 (stromal cell-derived factor 1α) secreted by tumor cells, as evidenced by blockage of CTL migration by Abs to CXCL12 or CXCR4, high concentrations of CXCL12 or small molecule CXCR4 antagonist. These studies, together with studies in mice indicating regression of CXCL12-transduced tumor cells, followed by regression of nontransduced challenge tumor cells, suggest that CXCL12 may be useful as an immunotherapeutic agent for cancer patients, when transduced into tumor cells, or fused to anti-tumor Ag Ab or tumor Ag.

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Potent Costimulation of Effector T Lymphocytes by Human Collagen Type I

Cited by 57 publications

References 33 publications

Functional Specialization of Memory Th Cells Revealed by Expression of Integrin CD49b

Functional Specialization of Memory Th Cells Revealed by Expression of Integrin CD49b

Migration of cytotoxic T lymphocytes toward melanoma cells in three‐dimensional organotypic culture is dependent on CCL2 and CCR4

CXC Chemokine Ligand 12 (Stromal Cell-Derived Factor 1α) and CXCR4-Dependent Migration of CTLs toward Melanoma Cells in Organotypic Culture

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