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Lymphocyte Trafficking (lymphocyte + trafficking)

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Medical Sciences100%

Selected Abstracts

Thermal Facilitation of Lymphocyte Trafficking Involves Temporal Induction of Intravascular ICAM-1

MICROCIRCULATION, Issue 2 2009
QING CHEN
ABSTRACT Objective: Fever is associated with improved survival, although its beneficial mechanisms are poorly understood. Previous studies indicate that the thermal element of fever augments lymphocyte migration across high endothelial venules (HEVs) of lymphoid organs by increasing the intravascular display of a gatekeeper trafficking molecule, intercellular adhesion molecule-1 (ICAM-1). Here, we evaluated the spatio-temporal relationship between the thermal induction of intravascular ICAM-1 and lymphocyte trafficking. Methods: Intravascular ICAM-1 density was quantified by immunofluorescence staining in mice exposed to fever-range whole-body hyperthermia (39.5±0.5°C). ICAM-1,dependent lymphocyte trafficking was measured in short-term homing assays. Results: A linear relationship was observed between the duration of heat treatment and intravascular ICAM-1 density in HEVs with maximal responses requiring sustained (i.e., five hours) thermal stress. Circulating lymphocytes were found to sense incremental changes in ICAM-1 on HEVs, such that trafficking is proportional to the intravascular density of ICAM-1. We further identified a hydroxamate-sensitive shedding mechanism that restores ICAM-1 expression to homeostatic levels following the cessation of thermal stress. Conclusions: The time-dependent response to thermal stress indicates that ICAM-1 density governs the efficiency of lymphocyte interactions with HEVs in vivo. These studies highlight the dynamic role of the microcirculation in promoting immune surveillance during febrile inflammatory responses. [source]

Prospective evaluation of intestinal homing memory T cells in ulcerative colitis

INFLAMMATORY BOWEL DISEASES, Issue 5 2004
A. L. Hart
Abstract Background: Intestinal homing (,7+) memory T cells reflect the mucosal environment in which they were primed. We hypothesized that prospective assessment of cytokine production by intestinal homing (,7+) memory T cells in ulcerative colitis patients followed from remission to early relapse may elucidate shifts in cytokine production relevant to the mucosal environment associated with the early phase of inflammation. Methods: Twelve patients with frequently relapsing ulcerative colitis (,2 relapses in the previous 12 months) were recruited in remission and followed prospectively until relapse. Antibody labeling of whole blood and flow cytometry were used to identify ,7+ cells and ,7, populations within CD3+CD45RA, leukocytes. Production of cytokines (IFN-,, TNF-,, IL-2, IL-10, TGF-,, and IL-4) was determined by intracellular labeling. Results: Early relapse of ulcerative colitis was associated with a shift of T cells from the naive to the memory T cell pool, and further the ratio of ,7+:,7, memory T cells was significantly reduced at relapse (p < 0.01). A greater proportion of intestinal homing ,7+ memory T cells produced IL-4 (p < 0.02) and TNF-, (p < 0.05) at disease relapse compared with remission. Non-intestinal homing ,7,memory T cells also showed a tendency toward an increased production of TH1 and TH2 cytokines. Conclusions: The earliest phase of intestinal inflammation in ulcerative colitis patients is associated with an increase in both TH1 (TNF-, and TH2 (IL-4) cytokines by intestinal homing ,7+ memory T cells. These data support the principles of targeting lymphocyte trafficking as therapies in ulcerative colitis. [source]

Thermal Facilitation of Lymphocyte Trafficking Involves Temporal Induction of Intravascular ICAM-1

MICROCIRCULATION, Issue 2 2009
QING CHEN
ABSTRACT Objective: Fever is associated with improved survival, although its beneficial mechanisms are poorly understood. Previous studies indicate that the thermal element of fever augments lymphocyte migration across high endothelial venules (HEVs) of lymphoid organs by increasing the intravascular display of a gatekeeper trafficking molecule, intercellular adhesion molecule-1 (ICAM-1). Here, we evaluated the spatio-temporal relationship between the thermal induction of intravascular ICAM-1 and lymphocyte trafficking. Methods: Intravascular ICAM-1 density was quantified by immunofluorescence staining in mice exposed to fever-range whole-body hyperthermia (39.5±0.5°C). ICAM-1,dependent lymphocyte trafficking was measured in short-term homing assays. Results: A linear relationship was observed between the duration of heat treatment and intravascular ICAM-1 density in HEVs with maximal responses requiring sustained (i.e., five hours) thermal stress. Circulating lymphocytes were found to sense incremental changes in ICAM-1 on HEVs, such that trafficking is proportional to the intravascular density of ICAM-1. We further identified a hydroxamate-sensitive shedding mechanism that restores ICAM-1 expression to homeostatic levels following the cessation of thermal stress. Conclusions: The time-dependent response to thermal stress indicates that ICAM-1 density governs the efficiency of lymphocyte interactions with HEVs in vivo. These studies highlight the dynamic role of the microcirculation in promoting immune surveillance during febrile inflammatory responses. [source]

Molecular Markers and Targeted Therapy of Skin Rejection in Composite Tissue Allotransplantation

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2010
T. Hautz
Skin rejection remains a major hurdle in reconstructive transplantation. We investigated molecular markers of skin rejection with particular attention to lymphocyte trafficking. Skin biopsies (n = 174) from five human hand transplant recipients were analyzed for rejection, characteristics of the infiltrate and lymphocytic adhesion markers. The cellular infiltrate predominantly comprised CD3+ T cells. CD68, Foxp3 and indoleamine 2, 3-dioxygenase expression and the CD4/CD8 increased with severity of rejection. Lymphocyte adhesion markers were upregulated upon rejection, intercellular adhesion molecule-1 and E-selectin correlated best with severity of rejection. Guided by the findings, a specific E- and P-selectin inhibitor was investigated for its effect on skin rejection in a rat hind limb allotransplant model. While efomycine M (weekly s.c. injection into the graft) alone had no effect, long-term allograft survival was achieved when combined with antithymocyte globulin and tacrolimus (control group without efomycine M rejected at postoperative day [POD] 61 ± 1). Upregulation of lymphocyte trafficking markers correlates with severity of skin rejection and time after transplantation in human hand transplantation. Blocking E- and P-selectin in the skin holds potential to significantly prolong limb allograft survival. [source]

Up-regulation of CCL17, CCL22 and CCR4 in drug-induced maculopapular exanthema

CLINICAL & EXPERIMENTAL ALLERGY, Issue 5 2007
B. Tapia
Summary Background Maculopapular exanthema has been reported to be the most frequently drug-induced cutaneous reaction. Although T lymphocytes are involved in the pathomechanism of this disease, little is know about the recruitment of these cells to the skin. Objective The aim of this work is to study the role of the chemokines TARC/CCL17 and MDC/CCL22 in the lymphocyte trafficking to affected skin in drug-induced exanthemas. Methods Real-time PCR was performed to quantify gene expression levels of CCL17, CCL22 and their receptor CCR4 in lesional skin biopsies and in peripheral blood mononuclear cells from patients. CCL27 and CCL22 proteins were detected in the skin by immunochemistry. Protein expression of CCR4 was determined by flow cytometry in peripheral blood lymphocytes. Functional migration assays to CCL17 and CCL22 were assessed to compare the migratory responses of peripheral blood lymphocytes from patients and healthy subjects. Results CCL17 and CCL22 were up-regulated in maculopapular exanthema-affected skin. CCR4 mRNA levels and protein expression were increased in peripheral blood mononuclear cells during the acute phase of the disease. The increased expression of the receptor was consistent with a higher response of peripheral blood lymphocytes to CCL17 and CCL22 compared with the migratory response in healthy donors. Conclusion TARC/CCL17 and MDC/CCL22 might cooperate in attracting T lymphocytes to skin in drug-induced maculopapular exanthemas. [source]