Selective antibody blockade of lymphocyte migration to mucosal sites and mast cell adhesion

Palecanda, Aiyappa; Marshall, Jean S.; Li, Xian Chang; Briskin, Michael; Issekutz, Thomas B.

doi:10.1002/jlb.65.5.649

Cited by 14 publications

(17 citation statements)

References 41 publications

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“…7, anti-P-and anti-E-selectin treatment had no effect on the accumulation of labeled T cells in the blood, spleen, cervical, axillary and mesenteric lymph nodes, and Peyer's patches. However, mAb to VLA-4 either alone or in the presence of E-and P-selectin blockade partially inhibited T cell homing to the mesenteric lymph nodes and abolished migration to Peyer's patches in accordance with the known dependence of migration to the gut-associated lymphoid tissues on the ␣ 4 integrin, ␣ 4 ␤ 7 (6,29,30).…”

Section: Effect Of Blocking E-and P-selectin and Vla-4 On T Lymphocytmentioning

confidence: 54%

The Role of E-Selectin, P-Selectin, and Very Late Activation Antigen-4 in T Lymphocyte Migration to Dermal Inflammation

Issekutz

2002

The Journal of Immunology

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T lymphocyte infiltration into inflamed tissues is thought to involve lymphocyte rolling on vascular endothelial cells. Because both selectin and α4 integrin adhesion molecules can mediate leukocyte rolling, the contribution of these receptors to lymphocyte migration to inflammation was examined. The recruitment of 111In-labeled spleen T cells to intradermal sites injected with IFN-γ, TNF-α, LPS, poly inosine-cytosine, and Con A was measured in the rat, and the effect of blocking mAbs to E-selectin, P-selectin, very late activation Ag-4 (VLA-4), and LFA-1 was determined on this T cell migration in vivo. Anti-E-selectin and anti-P-selectin mAbs each inhibited 10–40 and 20–48%, respectively, of the T lymphocyte migration to the inflammatory sites, depending on the stimulus. Blocking VLA-4 inhibited 50% of the migration to all of the lesions except Con A. Treatment with both anti-VLA-4 and anti-E-selectin mAbs inhibited up to 85% of the lymphocyte accumulation, while P-selectin and VLA-4 blockade in combination was not more effective than VLA-4 blockade alone in TNF-α, IFN-γ, LPS, and poly inosine-cytosine lesions. Inhibiting E-selectin, P-selectin, and VLA-4 together nearly abolished lymphocyte migration to all inflammatory sites. Anti-LFA-1 mAb strongly inhibited lymphocyte accumulation by itself, and this inhibition was not significantly further reduced by E- or P-selectin blockade. Thus, T cell migration to dermal inflammation is dependent on E-selectin, P-selectin, and VLA-4, likely because these three receptors are required for rolling of memory T lymphocytes, but VLA-4 and E-selectin are especially important for lymphocyte infiltration in these tissues.

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Section: Effect Of Blocking E-and P-selectin and Vla-4 On T Lymphocytmentioning

confidence: 54%

The Role of E-Selectin, P-Selectin, and Very Late Activation Antigen-4 in T Lymphocyte Migration to Dermal Inflammation

Issekutz

2002

The Journal of Immunology

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“…Cells were stained at 4° with the following mouse mAbs to rat antigens: W3/25 (anti‐CD4), MRC OX‐8 (anti‐CD8), MRC OX‐22 (anti‐CD45RC), MRC OX‐39 (anti‐CD25), R7·3 (anti‐β TCR) and NKR‐P1a (anti‐CD161a) from Serotec (Toronto, Ont., Canada). Mouse mAbs TA‐2 (anti‐α 4 ), TA‐5·1 (anti‐CD62 L ) and TA‐6 (anti‐β 7 ) were previously generated in our laboratory 27,32 , 33 . Chemokine receptors were stained with hamster anti‐CXCR6 and anti‐CXCR3 mAbs 34 .…”

Section: Methodsmentioning

confidence: 99%

“…Mouse mAbs TA-2 (anti-a 4 ), TA-5Á1 (anti-CD62 L ) and TA-6 (anti-b 7 ) were previously generated in our laboratory. 27,32,33 Chemokine receptors were stained with hamster anti-CXCR6 and anti-CXCR3 mAbs. 34 All primary mAbs were detected with appropriate conjugated polyclonal secondary Abs.…”

Section: Flow Cytometrymentioning

confidence: 99%

CXCR6 is expressed on T cells in both T helper type 1 (Th1) inflammation and allergen‐induced Th2 lung inflammation but is only a weak mediator of chemotaxis

Latta¹,

Karkada²,

Issekutz

2007

Immunology

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Summary Numerous chemokine receptors are increased in number on T cells in inflamed tissues. Our objective was to examine CXCR6 expression on lymphocytes during immune and inflammatory reactions and its potential for mediating T‐cell recruitment. The cDNA for rat CXCR6 was cloned and monoclonal antibodies (mAbs) to CXCR6 were developed. CXCR6 was present on 4–6% of CD4 and CD8 T cells in blood, normal lymph nodes (LNs) and the spleen, primarily on memory T cells. In vitro antigen re‐stimulation of LN T cells from animals with autoimmune arthritis and experimental autoimmune encephalomyelitis (EAE) increased the proportion of CXCR6+ T cells to 35–50% and anti‐T‐cell receptor (TCR) activation to 60–80%. In vivo, after antigen challenge of LNs there was only a small increase in CXCR6+ T cells on the lymphoblasts in the LNs, and a much higher percentage of T cells were CXCR6+ in virus‐induced peritoneal exudates (∼47%) and in allergen‐induced lung inflammation (33%). Chemotaxis of CXCR6‐expressing inflammatory T cells to CXCL16 was poor, but that to CXCL10 was robust. We conclude that few T cells in normal and antigen‐challenged LNs are CXCR6+, whereas a high proportion of in vitro activated T cells and T cells from inflammatory sites are CXCR6+, but these cells migrate poorly to CXCL16. This suggests that CXCR6 may contribute to T‐cell positioning and activation, rather than recruitment. CXCR6 is also expressed on T cells not only in T helper type 1 (Th1) inflammation (arthritis and EAE) but also, as shown here, in Th2 inflammation, where it is increased after allergen challenge.

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“…Connective tissue mast cells express substantially less VLA-4 [25]. Therefore, it is possible that mast cell accumulation in the cutaneous Arthus reaction is independent of the interaction between VCAM-1 and VLA-4.…”

Section: Leukocyte Infiltration In the Cutaneous Arthus Reactionmentioning

confidence: 99%

Intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 cooperatively contribute to the cutaneous Arthus reaction

Orito

Fujimoto

Ishiura

et al. 2007

Journal of Leukocyte Biology

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Immune complex-induced inflammation is mediated by inflammatory cell infiltration, a process that is highly regulated by expression of multiple adhesion molecules. The roles and interactions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), the major regulators of leukocyte firm adhesion, were examined in the cutaneous reverse passive Arthus reaction using ICAM-1-deficient (ICAM-1 -/-

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Selective antibody blockade of lymphocyte migration to mucosal sites and mast cell adhesion

Cited by 14 publications

References 41 publications

The Role of E-Selectin, P-Selectin, and Very Late Activation Antigen-4 in T Lymphocyte Migration to Dermal Inflammation

The Role of E-Selectin, P-Selectin, and Very Late Activation Antigen-4 in T Lymphocyte Migration to Dermal Inflammation

CXCR6 is expressed on T cells in both T helper type 1 (Th1) inflammation and allergen‐induced Th2 lung inflammation but is only a weak mediator of chemotaxis

Intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 cooperatively contribute to the cutaneous Arthus reaction

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