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Results for “Lymphopenia”

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At least 19 recordsLinked to original sources

PubMed2006

CD25+CD4+ regulatory T cells and memory T cells prevent lymphopenia-induced proliferation of naive T cells in transient states of lymphopenia.

Lymphopenia has been associated with autoimmune pathology and it has been suggested that lymphopenia-induced proliferation of naive T cells may be responsible for the development of immune pathology. In this study we demonstrate that lymphopenia-induced proliferation is restricted to conditions of extreme lymphopenia, because neither naive nor memory T cells transferred into T cell-depleted hosts proliferate unless the depletion exceeds 90% of the peripheral repertoire. Memory CD4 T cells as well as regulatory CD4 T cells proved to be relatively resistant to depletion regimes, and both subsets restrict the expansion and phenotypic conversion of naive T cells by an IL-7R-dependent mechanism. It therefore seems unlikely that lymphopenia-induced proliferation of peripheral T cells causes deleterious side effects that result in immune pathology in states of partial and transient lymphopenia.

Adoptive Transfer↗

PubMed2004

Long-term persistent lymphopenia in hematopoietic stem cell donors after donation for donor lymphocyte infusion.

OBJECTIVES: To analyze the consequences of lymphocyte donations on lymphopoiesis in donors having previously undergone hematopoietic stem cell collection for allogeneic stem cell transplantation. METHODS: Repeated analysis of leukocyte subsets in the peripheral blood of 76 hematopoietic stem cell donors undergoing lymphocyte donation(s) for DLI. RESULTS: Grade I/II lymphopenia was present in 22 donors (29%) just before first apheresis for lymphocyte collection, demonstrating that former stem cell donation induced prolonged lymphopenia in a subset of donors. The monocytic lineage was not affected. Older age and history of PBSC harvest constituted 2 independent factors of lymphopenia, but had no influence on monocytopenia. The first apheresis induced lymphopenia in 36 donors (47%) and monocytopenia in 23 donors (39%). Lymphopenia before first apheresis and prior history of PBSC harvest were independent factors of apheresis-induced lymphopenia while those factors had no influence on monocytopenia. A time-dependent decrease in lymphocyte counts was observed in donors undergoing repeated aphereses, resulting in persistent and prolonged lymphopenia in 50% of donors. No persistent monocytopenia over time and aphereses was observed. Kaplan-Meier estimate of the risk to develop persistent lymphopenia after multiple aphereses was 21% +/- 6% at 2 months, 38% +/- 8% at 4 months, and 64% +/- 10% at 12 months. After Cox regression analysis, previous PBSC harvest remained the unique factor associated with the risk for persistent lymphopenia. CONCLUSIONS: Monitoring the potential long-term effects of repeated aphereses in hematopoietic stem cell donors appears important. Selecting young bone marrow donors for subsequent DLI significantly reduces the risk for acute and prolonged lymphopenias.

Adolescent↗

PubMed1998

T lymphopenia in obese diabetic (db/db) mice is non-selective and thymus independent.

Although C57BL/KsJ db/db mice, an animal model of non-insulin-dependent diabetes mellitus (NIDDM), develop T lymphopenia in association with the progression of NIDDM, the T lymphopenia has not been fully investigated. In this study, to elucidate how and why T lymphopenia develops in db/db mice, T-lymphocyte subsets in spleen and thymus were longitudinally examined by flow cytometry and the effects of thymectomy and dietary restriction on the development of T lymphopenia were evaluated. After 8 weeks of age, when obese diabetes progresses, T lymphopenia in both spleen and thymus developed and all T-lymphocyte subsets examined were similarly reduced compared to lean (-/X) littermates, indicating non-selective T lymphopenia in db/db mice. Thymectomy performed at 5 wk of age, when neither T lymphopenia nor NIDDM yet presents, had no significant effect on the development of T lymphopenia. Furthermore, pair feeding until 30 weeks of age produced normal body weight and normoglycemia with still marked hyperinsulinemia, but failed to correct T lymphopenia in db/db mice. In conclusion, our results suggest that T lymphopenia may develop non-selectively and independently of either thymic dysfunction or obese diabetes in db/db mice.

Animals↗

PubMed2006

Systemic lupus erythematosus in a multiethnic US cohort, XXXVII: association of lymphopenia with clinical manifestations, serologic abnormalities, disease activity, and damage accrual.

OBJECTIVE: To determine if lymphopenia is associated with clinical/immunologic manifestations, disease activity, and disease damage in systemic lupus erythematosus (SLE). METHODS: The study group comprised 591 patients with SLE participating in a multiethnic, longitudinal outcome study. Cumulative clinical/immunologic (per American College of Rheumatology criteria) and pharmacologic treatment variables were obtained at enrollment (T0) and last visit (TL). Lymphopenia (<1,500/mm3) was scored only when clinically attributable to SLE and not to medications or other causes. Lymphocyte counts were expressed in 4 categories per the Systemic Lupus Activity Measure (SLAM): normal (> or =1,500/mm3), mild (1,000-1,499/mm3), moderate (500-999/mm3), and marked (<500/mm3). Disease activity was assessed with the SLAM and the Physician's Global Assessment (PGA). Disease damage was determined with the Systemic Lupus International Collaborating Clinics Damage Index (SLICC-DI). The relationship of lymphopenia with cumulative clinical/immunologic and pharmacologic treatment variables was first examined, then the association between the SLAM, PGA, and SLICC-DI scores with different categories of lymphopenia was examined by generalized estimating equation (GEE) regression analyses. Ethnicity, age, and sex were entered into all regression models. RESULTS: At T0 and TL, lymphopenia was found to be positively associated with renal involvement, leukopenia, anti-double-stranded DNA antibodies, anti-Ro antibodies, and the use of glucocorticoids, azathioprine, and methotrexate, but was negatively associated with photosensitivity. On GEE analyses, marked lymphopenia at T0 and moderate and marked lymphopenia for all visits were independently associated with higher SLAM, PGA, and SLICC-DI scores. CONCLUSION: Lymphopenia is associated with several clinical/immunologic manifestations in SLE. Moderate and marked lymphopenia are associated with higher disease activity and damage accrual.

Adult↗

PubMed1988

The contributions of adrenal hormones, hemodynamic factors, and the endotoxin-related stress reaction to stable prostaglandin analog-induced peripheral lymphopenia and neutrophilia.

Stable prostaglandin analogs are known to induce lymphopenia and neutrophilia in a dose-dependent fashion after subcutaneous injection in rats. The purpose of the present investigation is to determine whether the prostaglandin-induced changes in circulating leukocytes might be secondary to hypotension with the ensuing release of adrenal hormones. The adrenal medullary catecholamine epinephrine was found to induce neutrophilia in both intact and adrenalectomized rats, and the glucocorticosteroid analog dexamethasone induced a profound lymphopenia in rats as reported by previous investigators. A stable analog of PGF2 alpha (15-S-15-methyl PGF2 alpha; M-PGF2 alpha) at the dose of 1 mg/kg induced marked systemic hypotension 1 h after injection, with lymphopenia and neutrophilia 6 h after injection. The non-prostanoid hypotensive agent captopril, at a dose of 63 mg/kg, induced a hypotension of similar magnitude and kinetics to that induced by prostaglandin. Captopril also induced lymphopenia and neutrophilia at 6 h, although the neutrophilia was of lesser magnitude than that induced by prostaglandins. The prostaglandin-induced lymphopenia was found to be mediated, at least in part, by the hypotension-induced release of adrenal hormones, as evidenced by the abrogation of lymphopenia in prostaglandin-treated adrenalectomized rats. Captopril-treated adrenalectomized rats, however, did develop a significant lymphopenia, suggesting that hypotension can result in lymphopenia even in adrenalectomized rats. The M-PGF2 alpha-induced neutrophilia in adrenalectomized rats, by comparison to captopril-induced neutrophilia in adrenalectomized rats, was greater than the neutrophilia expected as the result of hypotension alone. Indeed, the M-PGF2 alpha-induced neutrophilia in adrenalectomized rats was greater than the captopril-induced neutrophilia in sham-adrenalectomized rats. Thus, a portion of the neutrophilia induced by M-PGF2 alpha in intact rats may be mediated through adrenal-independent, hemodynamic-independent mechanisms. The possibility that M-PGF2 alpha might be inducing neutrophilia via an endotoxin-like stress reaction was investigated by examining changes in circulating white blood cells in intact and adrenalectomized C3H/HeN (endotoxin-sensitive) and C3H/HeJ (endotoxin-resistant) mice after prostaglandin administration. No quantitative differences in the prostaglandin-induced neutrophilia were noted in C3H/HeJ mice as compared to the C3H/HeN mice.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenalectomy↗

PubMed2005

DR.lyp/lyp bone marrow maintains lymphopenia and promotes diabetes in lyp/lyp but not in +/+ recipient DR.lyp BB rats.

Lymphopenia is due to a frameshift mutation in Gimap5 on rat chromosome 4 and is linked to type 1 diabetes in the diabetes prone (DP) BB rat. The hypothesis that bone marrow derived cells confer the lymphopenia phenotype was tested by reciprocal bone marrow transplantation in 40-day-old lethally irradiated diabetes resistant (DR) congenic DR.lyp/lyp (lymphopenia and diabetes) and DR.+/+ (no lymphopenia and no diabetes) rats. In two independent series of transplants, all DR.lyp/lyp rats (n=5 and 4) receiving DR.lyp/lyp bone marrow retained lymphopenia and developed insulitis (5/5 and 4/4) as well as diabetes in some (2/5 and 3/4). Both DR.+/+ and DR.lyp/lyp rats receiving DR.+/+ bone marrow cells as well as DR.+/+ rats receiving DR.lyp/lyp bone marrow cells showed no lymphopenia or diabetes. In accordance with earlier studies in non-congenic BB rats, the DR.+/+ rats receiving DR.lyp/lyp bone marrow cells recapitulated an intermediary phenotype rather than the +/+ or lyp/lyp phenotypes. Our data demonstrate that BBDP rat lymphopenia and diabetes are transferred by bone marrow transplantation to syngeneic DR.lyp/lyp but not DR.+/+ recipients. The intermediary recapitulation of DR.lyp/lyp T cells in recipient DR.+/-/+/- rats suggests that radiation resistant +/-/+/- T cells, the Gimap5 mutation in bone marrow cells, or both may not support the development of lymphopenia.

Animals↗

PubMed1994

Prevalence of lymphopenia in children with AIDS.

Hematologic abnormalities, such as anemia, neutropenia, lymphopenia, and thrombocytopenia, are frequently observed in patients with acquired immunodeficiency syndrome (AIDS). While lymphopenia has been noted in up to 80% of adults, only 50% of children with AIDS are reported to be lymphopenic. We reviewed the blood counts of hospitalized children with AIDS to determine the frequency of lymphopenia and other hematologic abnormalities. Seventy-four children with AIDS (ages 4 months to 9.5 years) were admitted to Kings County Hospital Center (Brooklyn, New York) from January 1990 to March 1991; data consisted of 709 CBCs (range one to 39, median 11) from 176 admissions (range one to 15). In some patients admitted during the study period, charts from previous admissions were reviewed. Anemia (Hb less than than third percentile for age) was noted in 68 of 74 (92%) patients. Leukopenia (WBC less than 4000/mm3) was noted in 32 of 74 (43%) patients. Lymphopenia (lymphocyte counts below normal for age) was seen in 59 of 74 (78%) patients; of these, more than half (31 of 59) had persistently low absolute lymphocyte counts. Thrombocytopenia (platelet count less than 150,000/mm3) was seen in 20 of 74 (27%) and was found in four of eight patients who expired. Pancytopenia was seen in nine of 74 (12%) patients. Progression of hematologic abnormalities with anemia followed by lymphopenia, thrombocytopenia, and finally leukopenia was demonstrated in 22 patients. This review shows a prevalence of hematologic abnormalities that is similar to those of previous reports in children except for a considerably higher prevalence of lymphopenia. As expected, lymphopenia was a marker for disease progression.

Acquired Immunodeficiency Syndrome↗

PubMed2006

Type I interferons directly regulate lymphocyte recirculation and cause transient blood lymphopenia.

Early viral infection is often associated with lymphopenia, a transient reduction of blood lymphocyte counts long before the onset of clinical symptoms. We have investigated lymphopenia in mice infected with vesicular stomatitis virus (VSV) or treated with the Toll-like receptor (TLR) agonists poly(I:C) and R-848. In all cases analyzed, lymphopenia was critically dependent on type I interferon receptor (IFNAR) signaling. With the use of bone marrow-chimeric mice, radioresistant cells, such as stroma and endothelium, could be excluded as type I interferon (IFN-alpha/beta) targets for the induction of lymphopenia. Instead, adoptive transfer experiments and studies in conditionally gene-targeted mice with a B- or T-cell-specific IFNAR deletion demonstrated that IFN-alpha/beta exerted a direct effect on lymphocytes that was necessary and largely sufficient to induce lymphopenia. Furthermore, after treatment with R-848, we found that other cytokines such as TNF-alpha also played a role in T-cell lymphopenia. Investigation of the molecular mechanism revealed that lymphopenia was mainly independent of G protein-coupled receptors (GPCRs) and chemokines. In an adhesion assay, B cells of poly(I:C)-treated mice showed moderately increased adhesion to ICAM-1 but not to VCAM-1. In conclusion, our data identify a new effect of direct IFN-alpha/beta stimulation of lymphocytes that profoundly affects lymphocyte redistribution.

Animals↗

PubMed2026

Prognostic value of lymphopenia in early breast cancer: learnings from the prospective CANTO cohort.

BACKGROUND: Lymphopenia has been associated with poor outcomes in metastatic breast cancer (BC), but its prognostic relevance in early-stage disease remains unclear. This study aimed to evaluate the prognostic value of baseline lymphopenia in patients with non-metastatic BC using data from the prospective French CANTO cohort (NCT01993498). METHODS: 10,854 patients with baseline absolute lymphocyte count (ALC) were analysed. Lymphopenia was defined as ALC < 1.0 × 10⁹ cells/L, measured before any cancer treatment. Relapse-free survival (RFS), overall survival (OS), and treatment-related toxicities were assessed using Kaplan-Meier estimates, piecewise-Cox regression models, and cause-specific hazard analyses considering pre-specified time periods. RESULTS: Baseline lymphopenia was observed in 342 patients (3.1%). It was associated with ECOG performance status > 0, hypoalbuminemia, and prior neoplasia. Lymphopenia correlated with inferior 5-year RFS (89.1% vs. 92.9%) and OS (92.5% vs. 96.4%). In multivariable analyses, lymphopenia was associated with increased risk of early relapse during the first 24 months (HR = 2.11; 95%CI: 1.28-3.48; p = 0.003), but not beyond, and no independent prognostic impact on OS was observed. No significant differences were found in surgical complications or chemotherapy dose intensity, though granulocyte colony-stimulating factor use was higher among lymphopenic patients. CONCLUSION: Baseline lymphopenia is uncommon in early BC but may serve as a marker of early relapse risk. Although it does not independently predict long-term survival, its presence could reflect underlying tumour aggressiveness or patient frailty. These findings support further investigation of lymphocyte subpopulations to refine prognostic stratification in early BC. TRIAL REGISTRATION: Approved by French ethics committee in 2011 (ID-RCB:2011-A01095- 36,11-039 /NCT01993498 [20FEB2012]).

Adult↗

PubMed2004

Selective CD4+ lymphopenia in melanoma patients treated with temozolomide: a toxicity with therapeutic implications.

PURPOSE: Standard schedule temozolomide (TMZ; daily for 5 days every 4 weeks) is often used in melanoma patients, but phase III data show that it is no more effective than standard dacarbazine. Extended TMZ dosing regimens may be superior by delivering the drug continuously at a higher dose over time. Using an extended dosing schedule, we noted a high incidence of lymphopenia and occasional opportunistic infections (OIs). Here we report our retrospective experience in the first 97 patients. MATERIALS AND METHODS: TMZ was administered at 75 mg/m(2)/d orally for 6 weeks every 8 weeks, although nine patients were treated continuously without a break. Seventeen patients were treated with TMZ alone; 73 patients received TMZ with thalidomide; seven patients received TMZ with low-dose interferon alfa. RESULTS: Median duration of TMZ treatment was 113 days; 29% received > or = 24 weeks of therapy. Lymphopenia was seen in 60% of patients (absolute lymphocyte count < 800/microL) with a median of 101 days to lymphopenia. TMZ did not cause significant neutropenia or thrombocytopenia. Lymphopenia was not more common in patients treated concomitantly with thalidomide. In all patients analyzed for lymphocyte subsets, lymphopenia induced by TMZ affected the CD4(+) compartment preferentially. There were two documented OIs (Pneumocystis and Aspergillus pneumonia) as well as other infections indicative of T-cell dysfunction in another 21 patients. CONCLUSION: TMZ at this dose and schedule results in CD4(+) lymphopenia in a majority of patients that can result in OIs. Pneumocystis pneumonia prophylaxis should be considered for patients who develop sustained lymphopenia on TMZ.

Adult↗

PubMed2006

Autoimmunity during lymphopenia: a two-hit model.

The immune system has evolved elaborate mechanisms to respond to diverse antigens while minimizing the risk for autoimmune reactivity. During lymphopenia, however, some mechanisms that normally serve to maintain host tolerance are temporarily suspended. Peripheral T cells proliferate in response to self-antigens in lymphopenic hosts, but proliferation toward these same antigens is prevented when T cell numbers are normal. This process, termed homeostatic peripheral expansion, augments peripheral T cell number and limits repertoire skewing during recovery from lymphopenia and also predisposes lymphopenic hosts to autoimmune disease. This paper reviews murine and human settings in which autoimmunity occurs in the context of lymphopenia. We propose a two-hit model, in which lymphopenia plus another insult is sufficient to induce autoimmune disease. Among the secondary insults that appear sufficient to induce autoimmunity during lymphopenia are overproduction of IL-21 as occurs in the NOD.SCID mouse, depletion of Tregs as demonstrated in murine colitis and gastritis models, and tissue inflammation as seen in HIV infected patients who develop immune reconstitution inflammatory syndrome (IRIS). Delineating critical cofactors which result in autoimmune disease during lymphopenia can provide insight into the pathophysiology of naturally occurring autoimmune diseases as well as generating testable hypothesis for inducing tumor-specific autoimmunity in lymphopenic hosts with cancer.

Animals↗

PubMed1998

Clinical associations of lymphopenia in elderly persons admitted to acute medical and psychiatric wards.

Lymphopenia is a common finding in old people admitted to medical and psychiatric wards. We describe a pilot study of the clinical associations, and prognostic significance of lymphopenia in elderly persons admitted to acute medical and psychiatric wards. Consecutive patients admitted to acute medical and psychiatric wards were prospectively selected according to initial peripheral lymphocyte count (PLC) into lymphopenic (PLC < 1.0 X 10(9)/litre, n = 41), and non-lymphopenic (PLC > 1.5 x 10(9)/litre, n = 23). Results of routine haematological and biochemical investigations were recorded, as well as drug history and medical diagnoses. Anthropometric measurements, assessment of functional ability (Barthel ADL Index), and cognitive function (Mini-Mental State Examination) were then performed by investigators blind to lymphocyte status. Patients were contacted between 3 and 6 months following recruitment into the study. Lymphopenia was associated with functional ability as measured by a lower Barthel score (p = 0.004), and cognitive impairment as measured by the Mini-Mental State Examination (p = 0.02). No association was found with medical diagnostic groupings, drugs known to cause lymphopenia, nutritional status, or survival. Lymphopenia may be a significant marker of vulnerability, and a larger study is required to elucidate the veracity and mechanisms of lymphopenia-associated debility.

Aged↗

PubMed2006

Diminished expression of complement regulatory proteins (CD55 and CD59) in lymphocytes from systemic lupus erythematosus patients with lymphopenia.

CD55 and CD59 are glycophosphatidylinositol-anchored proteins with complement inhibitory properties. Lymphopenia in systemic lupus erythematosus (SLE) has been associated with autoantibodies targeting nuclear antigens. The aim of this study was to evaluate the surface density of CD55 and CD59 in T and B lymphocytes from patients with SLE and lymphopenia and its possible correlation with the presence of common SLE autoantibodies. Flow cytometric analyses were performed on CD55 and CD59 stained CD3+ and CD19+ cells from 40 SLE patients, 30 with lymphopenia and 10 without it, and 25 healthy controls. Autoantibodies were detected in the sera by enzyme linked immunosorbent assay. The mean fluorescence intensity of CD55 and CD59 in T and B cells was significantly diminished in SLE patients with lymphopenia when compared with healthy subjects. Interestingly, the opposite was found in T and B cells from non-lymphopenic SLE patients. Although there was no correlation between CD55 and CD59 surface density and the presence of any specificity of the autoantibodies tested, higher titres of anti-dsDNA, anti-SM and anti-ribosomal p antibodies were significantly associated with lymphopenia. The deficiency of CD55 and CD59 expression may play a role in the pathophysiology of lymphopenia, most likely by increasing the susceptibility of cells to complement mediated cytolysis.

Adult↗

PubMed1987

Recombinant human alpha lymphotoxin (tumor necrosis factor-beta) induces peripheral neutrophilia and lymphopenia in the rat.

Recombinant human alpha lymphotoxin (rLT) administered intravenously to Lewis rats induces peripheral neutrophilia and lymphopenia in a dose-response dependent fashion. A dose of 30,000 units of rLT induced a neutrophilia (1589 +/- 326 to 5554 +/- 1050 neutrophils/cu mm) and lymphopenia (10,368 +/- 992 to 4636 +/- 878 lymphocytes/cu mm) at 2 hours after injection that was highly significant (P less than 0.001 and P less than 0.001, respectively) in comparison with vehicle controls. The kinetics of the neutrophilia that peaked at 2 hours as well as of the lymphopenia were highly reminiscent of the neutrophilia and lymphopenia following intravenous administration of either recombinant human interleukin-1 (IL-1) alpha or beta to rats. The peripheral neutrophilia was accompanied by a significant depletion of bone marrow neutrophils (P less than 0.001), as is also known to occur after administration of IL-1. Systemic blood pressure was not affected by rLT, which suggested that the changes in circulating leukocyte subsets were not attributable to hemodynamic changes nor to the hemodynamic-change-related release of adrenal hormones. Adrenalectomy did not alter the rLT-induced neutrophilia or lymphopenia, which suggested that rLT does not mediate its hematologic effects on peripheral blood leukocytes via the release of adrenal hormones. Pretreatment of rats with dexamethasone, indomethacin, or aspirin also did not alter rLT-induced neutrophilia or lymphopenia, which suggested that rLT-induced hematologic effects were not mediated via arachidonic acid metabolites, in stark contrast to IL-1 induced neutrophilia, which is inhibited by both dexamethasone and indomethacin.

Animals↗

PubMed2001

Morbidity and mortality in rheumatoid arthritis patients with prolonged and profound therapy-induced lymphopenia.

OBJECTIVE: Therapies that deplete lymphocytes often improve symptoms in patients with otherwise refractory autoimmune disease but may result in long-term lymphopenia, the consequences of which are uncertain. To assess the impact of prolonged lymphopenia on morbidity and mortality, we studied patients who had previously received lymphocytotoxic monoclonal antibody (mAb) therapy for rheumatoid arthritis (RA). METHODS: Fifty-three patients who received the lymphocytotoxic mAb CAMPATH-1H between 1991 and 1994 in the United Kingdom were assessed for mortality and infectious and malignant morbidity, by interview and case-note review. In addition, patients were monitored via the National Health Service Central Registry, to verify notification of death. Peripheral blood lymphocyte subsets were analyzed by flow cytometry. A retrospective, matched-cohort study of mortality was also performed with 102 control subjects selected from the European League Against Rheumatism database, which comprises patients with rheumatic disorders who have received immunosuppressive drugs. RESULTS: There was profound and persistent peripheral blood lymphopenia in the mAb-treated patients, affecting predominantly the CD4+ subset. Median CD4+, CD8+, and CD19+ peripheral blood lymphocyte counts at 73-84 months after therapy were 185 cells/microl, 95 cells/microl, and 115 cells/microl, respectively. At a median followup of 71 months (range 14-90), 13 patients had died (24.5%), compared with 18% of the matched controls, providing a mortality rate ratio of 1.45 (95% confidence interval 0.65-3.13). During 283 patient-years of followup, there were 36 infections classified as major (12.7 per 100 patient-years). The causes of death and the spectrum of infections documented were similar to those expected in a hospital-based RA cohort. Patients who received more than 1 course of therapy had more severe lymphopenia than did patients who received a single course, but this did not have an impact on mortality or morbidity. CONCLUSION: Despite the occurrence of profound and long-lasting lymphopenia following treatment with antilymphocyte mAb therapy for RA, this therapy is not associated with a large excess of mortality nor with an unusual spectrum of infections, at least during a medium-term period of followup. These data are also relevant to patients receiving lymphocytotoxic mAb therapy for other indications, and to patients receiving other lymphodepleting therapies such as autologous stem cell transplantation.

Aged↗

PubMed1989

The gene for the T lymphocyte alloantigen, RT6, is not linked to either diabetes or lymphopenia and is not defective in the BB rat.

In an outcross between a diabetic BB/H rat and a healthy Long Evans Hooded rat, the segregation of the RT6 gene was studied in the 207 F2 animals to look for linkage with diabetes or lymphopenia. The recessive gene, albino (c), was used as a marker for the RT6 gene because of the close proximity of these two genes on chromosome 1. Though most of the albino F2 rats should have been homozygous for the BB RT6 gene, we found no increase in the incidence of diabetes or lymphopenia among them when compared to their hooded littermates. Therefore, the RT6 gene was not linked to diabetes or lymphopenia in the BB rat. Moreover, the non-lymphopenic albino rats displayed normal RT6 expression when compared to the normal hooded rats showing that the RT6 gene from the BB/H grandfather was not defective. Any alteration in lymphocyte composition which could be specifically related to diabetes was studied by measuring all F2 rats for the major lymphocyte subsets including the RT6+ subset. We found that the typical pattern of lymphopenia described in diabetic BB rats was displayed by both diabetic and non-diabetic lymphopenic rats in the F2 generation. Thus, all these lymphocyte abnormalities including the depletion in RT6+ T lymphocytes appeared as a consequence of lymphopenia alone and could not be specifically related to diabetes.

Animals↗

PubMed1982

Lymphopenia and abnormal lymphocyte subsets in the "BB" rat: relationship to the diabetic syndrome.

The "BB" rat spontaneously develops insulitis followed by impaired glucose tolerance (IGT) and/or an insulin-dependent diabetic syndrome like that in man. All diabetic rats in this study showed marked lymphopenia in blood, lymph nodes, spleen, and thymus. Peripheral blood lymphopenia antedated glucoregulatory disturbances. All rats showing either insulitis with or without IGT or diabetes were lymphopenic. None with normal lymphocyte counts developed any abnormality. Diabetics showed marked decrease in the proportions of T+ lymphocytes in all tissues. The proportion of B (Ia+) lymphocytes was normal in blood, spleen and thymus, but increased in lymph nodes. However, in absolute terms both T and Ia+ lymphocytes were decreased. The subset decreased by the greatest proportion in all tissues was that which includes helper T lymphocytes. Thus: a) generalized lymphopenia most marked for T lymphocytes has been shown, b) helper T lymphocytes show proportionally the greatest reduction, c)thymic helper T deficit suggests a thymic origin of the lymphopenia, d) lymphopenia is a possible marker for susceptibility to the syndrome.

Animals↗

PubMed2005

Prolonged lymphopenia, lymphoid depletion, and hypoprolactinemia in children with nosocomial sepsis and multiple organ failure.

Lymphopenia and lymphoid depletion occur in adults dying of sepsis. Prolactin increases Bcl-2 expression, suppresses stress-induced lymphocyte apoptosis, and improves survival from experimental sepsis. We hypothesized that prolonged lymphopenia, lymphoid depletion, and hypoprolactinemia occur in children dying with sepsis and multiple organ failure (MOF). Fifty-eight critically ill children with and 55 without MOF admitted to a university hospital pediatric intensive care unit were enrolled in a prospective, longitudinal, observational clinical study. Prolactin levels and absolute lymphocyte count were measured on days 1, 3, 7, 14, and 21. Lymph node, thymus, and spleen autopsy specimens were examined for lymphoid depletion, with immunohistochemical staining for CD4, CD20, and CD21 and for lymphoid apoptosis. Prolonged lymphopenia (absolute lymphocyte count < 1000 for >7 days) occurred only in children with MOF (29 vs 0%, p < 0.05) and was associated independently with nosocomial infection (odds ratio (OR), 5.5, 95% confidence interval (CI), 1.7-17, p < 0.05), death (OR, 6.8, 95% CI, 1.3-34, p < 0.05), and splenic and lymph node hypocellularity (OR, 42, 95% CI, 3.7-473, p < 0.05). Lymphocyte apoptosis and ante/postmortem infection were observed only in children with lymphoid depletion. Prolonged hypoprolactinemia (>7 days) was more common in children with MOF (17 vs 2%, p < 0.05) and was associated independently with prolonged lymphopenia (OR, 8.3, 95% CI, 2.1-33, p < 0.05) and lymphoid depletion (OR, 12.2, 95% CI, 2.2-65, p < 0.05). Prolonged lymphopenia and apoptosis-associated depletion of lymphoid organs play a role in nosocomial sepsis-related death in critically ill children. Prolonged hypoprolactinemia is a previously unrecognized risk factor for this syndrome.

Adolescent↗