Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study examined the relationship between exercise-induced changes in the concentration of circulating immunocompetent cells and their surface expression of adhesion molecules: L-selectin (CD62L) and three beta 2-integrins [LFA-1(CD11a/CD18), Mac-1 (CD11b/CD18), and p150/95(CD11c/CD18)]. Eight young male volunteers exercised on a cycle ergometer for 60 min at 60% maximal oxygen uptake. Peripheral blood samples, collected every 30 min throughout exercise and during the 2-h recovery period, were used for flow-cytometric analysis. The experimental results were compared with control data obtained ever 60 min at corresponding times of the nonexercise day. The exercise regimen induced a granulocytosis and a lymphocytosis, mainly due to an elevation of CD8+ and CD16+ cells. During recovery, a further granulocytosis occurred but accompanied by a lymphopenia. The increased CD8+ cell-count during exercise was characterized by a selective mobilization of the CD62L- and CD11ahigh cells, i.e. primed CD8+ cells. A postexercise suppression of CD4+ cell-count was derived only from CD62L+ cells. The CD11b+ and CD11c+ lymphocytes also increased during exercise, largely attributable to an increase in CD16+ cells which co-expressed CD11b and CD11c molecules. The CD62L surface density of granulocytes increased significantly during recovery. This resulted from a selective influx of CD62Lhigh granulocytes into the circulation. There were no significant changes in per-cell density of the three beta 2-integrins on granulocytes and lymphocytes throughout the experimental period. These results suggest that the cell-surface expression of CD62L (and CD11a) molecules is associated with the differential mobilization of CD8+ cells during exercise, the postexercise suppression of CD4+ cell-counts and the granulocytosis following exercise.
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PMID:Exercise-induced changes in the expression of surface adhesion molecules on circulating granulocytes and lymphocytes subpopulations. 758 96

2-Acetyl-4(5)-(1,2,3,4-tetrahydroxybutyl) imidazole (THI) is an immunomodulatory compound which causes a reversible lymphopenia in mice by an unknown mechanism. In this study, we investigated the whereabouts of cells lost from the blood and the spleen during THI treatment Homing studies following is injection of fluorescently labelled splenocytes into THI-pretreated recipients showed that THI increased labelled cells in the liver, lungs and kidneys of THI-treated mice. Furthermore, the sequestration in the liver occurred just 1.5 h after injection of labelled cells with the increase still being present at 24 h after injection. Microscopic examination of liver sections indicated that fluorescent lymphocytes were clustered within the liver sinusoids in THI-treated mice, possibly associated with endothelial cells. The liver retention of lymphocytes was confirmed by immunohistochemical studies which showed a significant increase of T cells in the liver of THI-treated mice. To determine the subset of lymphocytes which are lost from the spleen and sequestered in non-lymphoid organs, lymphocytes remaining in the spleen after THI treatment were characterized. Our results confirmed that THI reduced B cells, CD4+ and CD8+ T cells and cells expressing CD62L, CD44 and IL-2R in the spleen.
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PMID:The immunomodulatory compound 2-acetyl-4-tetrahydroxybutyl imidazole causes sequestration of lymphocytes in non-lymphoid tissues. 942 99

Emotions and the neuroendocrine system are known to affect leukocyte distribution. However, there have so far been few reports on the relationship between hypothalamically induced emotional behavior and the endocrine-immune response. We previously reported changes in the leukocyte distribution and adhesion molecules induced by anteromedial hypothalamus stimulation (AH stimulation), which elicits restlessness behaviors in the cat. In this study, we examined ventromedial hypothalamus stimulation (VMH stimulation), which elicits threat behaviors. In addition, the endocrine responses after VMH stimulation were evaluated. VMH stimulation as well as AH stimulation induced elevations of plasma cortisol and epinephrine levels and granulocytosis and lymphopenia. In contrast, VMH stimulation induced only an elevation of plasma norepinephrine and elicited an opposite pattern of CD62L expression on the leukocyte subpopulations. The different endocrine-immunological reactions between VMH stimulation and AH stimulation were thus associated with different types of behavioral responses.
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PMID:Changes in the leukocyte distribution and surface expression of adhesion molecules induced by hypothalamic stimulation in the cat. 1209 83

Social stress of group-housed male mice induced a state of functional glucocorticoid (GC) resistance in splenocytes. The following studies examined the effects of paired-fighting (PF) stress on immune cell distribution and function in spleens of male mice. Following six daily PF stress sessions, splenic monocytes and neutrophils increased and lymphocytes decreased. PF also altered the distribution of CD62L and CD11b positive monocytes. Additionally, PF augmented proliferation and lowered the sensitivity of LPS-stimulated splenocytes to the antiproliferative effects of corticosterone, suggesting that PF induced a state of GC resistance in splenocytes. Together, these findings indicate that social stress altered phenotype and function of splenic immune cells. These findings may have implications for the healing of bite wounds that are often associated with social stress in rodents.
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PMID:Social stress alters splenocyte phenotype and function. 1241 35

Extracorporeal support during cardiac surgery initiates an inflammatory response, causing damage to cardiac, pulmonary and renal tissue [Post Pump Syndrome (PPS)]. This is accompanied by a neutrophil leucocytosis and lymphopenia, but less is known about the role of monocytes and markers of monocyte activity. We studied 19 patients undergoing cardiac surgery, obtaining blood samples from the aortic root (AR) and from the coronary sinus ( < s) before the cardiopulmonary bypass (CPB), 1 min after release of the aortic crossclamp and 10 min after weaning from CPB (periods 1, 2 and 3). Leucocyte count, monocyte count and HLA-DR, CD15, CD11b and CD62L activation markers were measured. In samples obtained from the coronary sinus (CS), HLA-DR, expressed as a percentage of the monocyte count, decreased between periods 1, 2 and 3 by 78%, 66% and 43%, respectively. A similar change was observed in samples from the AR. Conversely, CD62L increased in the CS samples (55%, 68% and 73%), but revealed a lesser increase in the AR samples (51%, 68% and 63%). The other markers showed little change throughout the procedure. Reduced immunological competence could result from the decrease in HLA-DR counts. Increases in CD62L sensitizes monocytes to the tethering effects of endothelial integrins and might contribute to the atherosclerotic process.
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PMID:Monocyte activation markers during cardiopulmonary bypass. 1286 85

The Biobreeding diabetes-prone rat suffers from a profound peripheral lymphopenia and yet succumbs to a T cell-dependent autoimmune disease. Lymphopenia segregates with a mutated chromosomal locus, termed lyp, recently identified as a frameshift mutation in IAN4. Others have correlated loss of IAN4 function with decreased mitochondrial integrity resulting in T cell apoptosis. Here we report that IAN4-/- T cells enter a state similar to that of partial activation wherein they down-regulate CD62L and undergo incomplete blasting yet do not progress through mitosis. When given a strong stimulus, this partial activation phenotype can be overcome. This phenotype can be recapitulated in wild-type T cells through suboptimal stimulation. The phenotype is not simply a reaction to the lymphopenic environment, as spontaneous CD62L down-regulation occurs in mature single-positive medullary thymocytes that develop within a non-lymphopenic environment, and normal T cells do not undergo similar blasting when parked in a lymphopenic environment. Finally, we show that IAN4-/- T cells are more readily triggered via TCR stimulation. Thus, in addition to their role in apoptosis, IAN family members may also play a role in regulating the T cell activation state through modulation of TCR signaling strength.
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PMID:Partial activation precedes apoptotic death in T cells harboring an IAN gene mutation. 1530 72

We compared the kinetics of T-cell recovery after extensive ex vivo and in vivo T-cell depleted autologous stem cell transplantation (SCT) for multiple sclerosis (MS; n=8) with unmodified SCT for hematological malignancies (HM; n=39). Both patient group showed a very protracted recovery of 'naive' CD4(+), 45R0(-) ( approximately CD45RA(+)) T-cells. Within the 'primed' CD4(+), 45R0(+) T-cells, the 'central memory' cells expressing the CD62L and CD27 markers were the slowest to recover. The repopulating T-cells were highly activated, as shown by increased expression of HLA-DR and the apoptosis marker CD95. The capability of CD4(+) and CD8(+) T-cells to produce IFN-gamma, IL-2 and TNF-alpha had reached normal ranges from 2 months post SCT onwards. Unexpectedly, the kinetics of T-cell recovery between 3 and 12 months post transplant was similar in T-depleted and unmodified SCT. Before SCT, the HM patients showed lymphopenia of all T-cell subsets, upregulated HLA-DR and CD95 expression and increased cytokine responses. We suggest that the similar kinetics of T-cell recovery in the two patient groups may be explained by the susceptibility to apoptosis of the activated CD4(+) T-cells in the autografts of the HM patients. This susceptibility to apoptosis would interfere with a swift and sustained CD4(+) T-cell regeneration post SCT.
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PMID:T-lymphocyte reconstitution following rigorously T-cell-depleted versus unmodified autologous stem cell transplants. 1651 23

Autologous transfer of anti-CD3/anti-CD28 (CD3/CD28)-activated CD4(+) T cells may benefit patients receiving autologous stem cell transplant with severe CD4 lymphopenia. Interleukin (IL)-15, an IL-2-like cytokine that promotes T cell survival may enhance immune reconstitution in conjunction with adoptive immunotherapy. We investigated the effect of IL-15 on effector and regulatory function of CD3/CD28-activated CD4(+) T cells. IL-15 upregulated CD45RO and CD25 whereas it down regulated CD62L expression of CD3/CD28-stimulated CD4(+) T cells. Both type 1 (IFN-gamma, tumor necrosis factor (TNF)-alpha) and type 2 (IL-5 and IL-10) production by CD3/CD28-activated CD4(+) T cells was further enhanced by IL-15. Co-culture experiments revealed that CD3/CD28-activated CD4(+) T cells down regulated proliferation of autologous peripheral blood lymphocytes (PBLs) and CD8(+) PBL subsets upon TCR ligation, a contact-dependent effect that was further enhanced by pretreatment with IL-15. Flow cytometric analysis of cell mixture with carboxyfluorescein diacetate succinimidyl ester and Annexin-V-PE staining revealed that CD3/CD28+IL-15-activated CD4(+) T cells showed increased apoptosis over CD4(+) T cells stimulated with CD3/CD28 alone. Taken together, pretreatment of CD3/CD28-activated CD4(+) T cells with IL-15 may increase regulatory function but may aggravate activation-induced apoptosis of CD3/CD28 CD4(+) T cells.
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PMID:Effect of interleukin-15 on effector and regulatory function of anti-CD3/anti-CD28-stimulated CD4(+) T cells. 1656 41

The sphingosine-1-phosphate receptor agonist FTY720 induces lymphopenia by inhibiting lymphocyte egress from thymus and lymph nodes. The immediate effect of the drug on T cells in blood and lymphoid tissues is well documented, however effects on peripheral T cell sub-populations have not been studied. We therefore analyzed the changes in T cell subset compositions in liver, lung, kidney, spleen, lymph nodes and blood induced by FTY720-treatment using 9-parameter flow cytometry. In untreated mice, naive T cells were present in all peripheral organs. Naive T cells were depleted from peripheral organs within 3 days by FTY720, and with slower kinetics from lymphoid organs. Antigen-experienced T cell subsets were less affected by FTY720-treatment and substantial numbers were retained in the periphery. The proportion of CD8(+)CD44(+)CD43(+) Gr-1(+) effector memory cells increased after FTY720-treatment, while that of CD8(+)CD44(+)CD62L(+) central memory cells was unchanged. Our data demonstrate that naive T cells pass peripheral tissues as part of their default recirculation pathway. FTY720 treatment primarily affects the recirculation of naive and central memory cells, both of which re-circulate through lymph nodes on a regular basis, but does not influence effector memory cells. This suggests that treatment with FTY720 may not interfere with immune functions mediated locally by tissue-resident peripheral effector/memory T cells.
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PMID:FTY720 preferentially depletes naive T cells from peripheral and lymphoid organs. 1716 43

Although T cell dysfunction and lymphopenia are key features of immunodeficient patients with the Wiskott-Aldrich syndrome and Wiskott-Aldrich syndrome protein (WASP)-deficient mice, T cell development appears relatively normal. We hypothesized that N-WASP, a ubiquitously expressed homologue of WASP, may serve a redundant function with WASP. To examine the unique and redundant activities of WASP and N-WASP, we generated ES cells devoid of WASP and N-WASP [double knockout (DKO)] and used the RAG-2-deficient blastocyst complementation system to generate DKO lymphocytes. Moreover, we mated WASP KO mice with mice containing a conditionally targeted N-WASP allele and used the Cre-loxP system to generate mice lacking WASP and N-WASP in T cells [conditional DKO (cDKO)]. In both systems, N-WASP-deficient cells were indistinguishable from WT cells. In contrast, T cell development in DKO and cDKO mice was markedly altered, as shown by thymic hypocellularity and reduced numbers of peripheral T cells. We found that the combined activity of WASP and N-WASP was important for CD4(-)CD8(-) double-negative (DN)-to-CD4(+)CD8(+) double-positive (DP) cell transition, and this may be partly explained by reduced cycling DN3 cells. In addition, decreased migratory responses of CD4(+)CD8(-) and CD4(-)CD8(+) single-positive (SP) cells and increased percentage of CD69(low)CD24(low) and CD62L(low) SP cells in cDKO cells imply retention of SP cells in the thymus. In summary, this study suggests that, although WASP serves a unique role for peripheral T cell function, T cell development depends on the combined activity of WASP and N-WASP.
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PMID:Wiskott Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development. 1787 99


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