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PubMed1996

An unusual association of Felty syndrome and TCR gamma delta lymphocytosis.

Felty syndrome, comprised of neutropenia, rheumatoid arthritis and splenomegaly, occurs in approximately 1% of patients with rheumatoid arthritis. Up to one third of these patients have an increased number of large granular lymphocytes. The usual immunophenotype of these cells is CD3+, CD8+, CD57+, T cell receptor (TCR) alpha beta. A patient with Felty syndrome and large granular lymphocytosis, who had an unusual immunophenotype CD3+, CD4-, CD8-, TCR gamma delta, is described. Her neutropenia responded to treatment with granulocyte colony stimulating factor (G-CSF), which was given in order to raise her neutrophil count prior to bilateral knee replacement surgery. Thus, Felty syndrome with large granular lymphocytosis is a heterogeneous condition, one in which TCR gamma delta large granular lymphocytosis may be found, and also shows a response to treatment with G-CSF.

Adult↗

PubMed1997

Invasive thymoma with CD4+CD8+ double-positive T cell lymphocytosis.

Lymphocytosis in the peripheral blood is a very rare manifestation of thymoma. A 45-year-old man presented with a giant mediastinal mass involving pleural dissemination and peripheral T cell lymphocytosis. Biopsy of the mediastinal mass revealed invasive thymoma, and two-color analysis of peripheral lymphocytes showed a marked increase in CD4+CD8+ double-positive cells. Both thymoma and lymphocytosis were improved by a combination of chemotherapy and mediastinal irradiation.

CD4 Antigens↗

PubMed1985

Persistent lymphocytosis: an unusual feature in sarcoidosis.

Persistent lymphocytosis as a presenting sign in sarcoidosis is described in a 61-year-old man. Lymphocytosis is an unusual finding in sarcoidosis. The case presented seems to suggest that sarcoidosis should be considered in the differential diagnosis of lymphocytosis.

Diagnosis, Differential↗

PubMed1993

Tissue infiltration in a CD8 lymphocytosis syndrome associated with human immunodeficiency virus-1 infection has the phenotypic appearance of an antigenically driven response.

HIV-1 infection may initiate to an HLA-associated response designated diffuse infiltrative lymphocytosis syndrome, characterized by increased numbers of circulating CD8 T cells that infiltrate salivary glands, lungs, gastrointestinal tract, and kidneys. Since this response could either be an antigenically driven process induced by HIV-1 or a lymphoproliferation of cells with neoplastic or unusual features, we sought to define the phenotype of the cellular populations, the nature of tissue derangement, and the tissue localization of virus in diffuse infiltrative lymphocytosis syndrome. Circulating CD8 T cells were greatly increased while CD4 T cell numbers remained in the range found in asymptomatic seropositive persons. The majority of CD8 and CD4 T cells in both blood and tissues had the memory phenotype of CD29+ (beta 1 integrin) and CD11a+/CD18 (beta 2 integrin) expression, but lacked markers of recent activation. A proportion of the circulating CD8 T cells also expressed CD57 (Leu 7) but not other markers of natural killer cells. HIV-encoded proteins were identified in tissue macrophages located in periacinar areas of the salivary glands. CD54 (intercellular adhesion molecule-1), a ligand for the CD11a integrin, was strongly expressed on postcapillary venule endothelium within lymphoid foci, and HLA-DR molecules were found on limited regions of ductular epithelium adjacent to lymphoid aggregates. These findings suggest that (a) the visceral lymphocytic infiltration in diffuse infiltrative lymphocytosis syndrome is an antigen-driven, and MHC-determined, host immune response to an element associated with HIV-1 infection, and (b) that the specific adhesive molecule interactions mediating the cellular influx, as well as the subsequent tissue damage, reflect altered patterns of gene expression in tissues undergoing an immune response.

AIDS-Related Complex↗

PubMed1993

Erythroderma and marked atypical lymphocytosis mimicking cutaneous T-cell lymphoma probably caused by phenobarbital.

A 56-year-old man had been treated with phenobarbital seven weeks prior to admission. One month after initiation of administration of phenobarbital, fever, skin rash and lymphadenopathy occurred. Nine days later, marked atypical lymphocytosis, eosinophilia and hepatic injury was noticed. The histology of the biopsied skin was indistinguishable from lymphoma. CHOP-therapy was started but the patient was followed without further treatment because of polyclonal T-lymphocytosis. Afterward, clinical and hematologic improvement ensued and he has been well until now, 52 months later. The marked T-lymphocytosis observed in this case is probably a lymphoid leukemoid reaction secondary to hypersensitivity to phenobarbital.

Dermatitis, Exfoliative↗

PubMed2001

[Acute infectious lymphocytosis associated to Giardia lamblia and Blastocystis hominis coinfection].

Acute infectious lymphocytosis is characterized by marked peripheral blood lymphocytosis, often associated with a mild, nonspecific febrile illness. We present a 4-year-old girl with acute infectious lymphocytosis associated with Giardia lamblia and Blastocystis hominis coinfection. Analysis of peripheral lymphocyte markers showed overall proliferation of B and T cells with a reduction in the proportion of T cells, especially in the CD4T cell subpopulation. Hematologic values returned to normal after treatment with metronidazole.

Acute Disease↗

PubMed1992

Demonstration of clonality, by X-linked DNA analysis, in chronic natural killer cell lymphocytosis and successful therapy with oral cyclophosphamide.

The expanded lymphocyte population in large granular lymphocyte (LGL)-leukemia carries the phenotypic characteristics of either cytotoxic T lymphocytes (CD3+,CD8+) or natural killer (NK) cells (CD3-,CD15+). In the former subset, clonality has been demonstrated by T-cell receptor gene rearrangement studies. Since NK cells do not rearrange T-cell receptor genes, the neoplastic nature of chronic NK cell lymphocytosis has not been well defined. We used X-linked DNA analysis to study the clonal nature of an expanded NK cell population in a patient with a 3-year history of relative lymphocytosis associated with anemia and neutropenia. Southern blot analysis showed no clonal T-cell receptor gene rearrangement. The majority of the circulating lymphocytes had a NK cell phenotype and demonstrated both direct NK cell-mediated cytotoxicity and antibody-dependent cellular cytotoxicity. However, the in vitro growth characteristics of these cells did not suggest that they were polyclonal expansions of normal NK cells. To determine directly the clonal origin of these cells, we performed X-linked DNA analysis. Density gradient centrifugation methods were used to isolate mononuclear cells, and NK cells were positively selected by CD16-immunoconjugated magnetic beads. The DNA of these cells was analyzed by restriction fragment length polymorphism-methylation strategy and showed a monoclonal pattern of X-chromosome inactivation while a polyclonal pattern was obtained in corresponding skin tissue. Treatment of the patient with oral cyclophosphamide resulted in complete hematologic remission. We conclude that chronic NK lymphocytosis may be clonal and responsive to immunosuppressive therapy.

Aged↗

PubMed1992

[A case of pulmonary sarcoidosis with B lymphocytosis in peripheral blood].

A 24-year-old man was admitted on October 14, 1988, with bilateral cotton-like shadows on chest X-ray film. Chest CT demonstrated multiple nodular shadows in bilateral lung fields. Laboratory data on admission showed peripheral blood lymphocytosis and slight decrease of serum IgG and IgA. ACE was within normal limits, and BALF findings showed no increase of lymphocytes. Surface marker analysis of peripheral blood lymphocytes showed an increase of B lymphocytes of antibody independent stage (B1, B4, J5, OKB7, sIgM, and sIgD positive cells were increased). Southern blot analysis of peripheral blood showed no rearrangement of immunoglobulin chains (H chain and L chain). In order to differentiate sarcoidosis from lymphoproliferative disorder, open lung biopsy was performed. Pathologic study revealed multiple epithelial granulomas without caseation. Immunohistochemical study demonstrated no accumulation of B cells of the lung. This patient was pathologically diagnosed as having pulmonary sarcoidosis. The abnormal chest shadows gradually improved without therapy; however, B cell lymphocytosis and slight decrease of serum IgG and IgA persisted. In general, lymphocytopenia of peripheral blood is usual in sarcoidosis. We report a rare case of pulmonary sarcoidosis with polyclonal B lymphocytosis of antibody independent stage in peripheral blood.

Adult↗

PubMed1991

[Rheumatoid arthritis and chronic granular T-cell lymphocytosis with neutropenia. A clinical condition distinct from Felty's syndrome].

103 cases of rheumatoid arthritis who had been diagnosed between 1984 and 1985 have retrospectively been analyzed, in order to identify those patients who had presented with associated neutropenia and in whom it was thus possible to suggest a presumptive diagnosis of either Felty's syndrome or chronic granulated lymphocytosis with neutropenia. Four patients (3.8%) satisfied the clinical criteria for the latter diagnosis while only one had typical Felty's syndrome. They were again studied using blood counts, microscopy of bone marrow and surface antigen analysis of mononuclear cells and the above mentioned diagnoses were confirmed. Though clinically indistinguishable, these two conditions are clearly distinct on both hematologic and immunological grounds. The four patients with rheumatoid arthritis and chronic granulated T cell lymphocytosis with neutropenia represent 36.3 per cent of our institution's patients with chronic granulated T cell lymphocytosis of undetermined significance. Caution should be used in the treatment of rheumatoid arthritis of the patients with associated granular lymphocyte proliferation, considering the possible adverse effects that drugs such as gold salts, penicillamine, cyclosporine and methotrexate may exert not only on the immunological system but also on granulocytopoiesis.

Adult↗

PubMed1990

Transient stress lymphocytosis during crisis of sickle cell anemia and emergency trauma and medical conditions. An immunophenotyping study.

Transient absolute lymphocytosis of peripheral blood has been described in "stress"-related emergency trauma and medical conditions. There are no reports of this phenomenon in patients with sickle cell anemia with vaso-occlusive crisis. We studied initial and follow-up immunophenotypic characteristics of 10 adult patients with sickle cell anemia in crisis and 15 adult patients with emergency conditions who presented with absolute lymphocytosis. On admission, both groups demonstrated increases in the numbers of CD20+ B cells and T cells of the CD2, CD4, CD8, and CD56 (NKH-1) phenotypes compared with control values. Findings in both groups of patients mimicked the results of parenteral epinephrine administration: a pan-B and -T lymphocytosis with marked increase in CD56 (fourfold to fivefold) and CD8 cells (threefold to fourfold) as well as moderate increases in CD20 and CD4 cells (twofold), resulting in a decrease in the CD4/CD8 ratio compared with control values. In patients with sickle cell anemia, there was an expected increase in the CD56 and CD4 populations; however, CD8 cells only doubled at the time of crisis. Therefore, the CD4/CD8 ratio was normal compared with control values. CD20+ B cell numbers exceeded those seen in the patients with medical and trauma emergencies. Elevated corticosteroid levels have been measured after injury in previous studies. Parenterally administered cortisol produces a lymphocytopenia after 4 to 6 hours that selectively decreases T cells. At 10 to 38 hours after admission, there was a marked reduction in the number of T cells in both groups of "stressed" patients, probably reflecting at least partial effects of endogenous corticosteroids. In contrast to the patients with medical and trauma emergencies, the mean lymphocyte count in the patients with sickle cell anemia remained elevated in the "high normal" range and consisted of increased numbers of B cells and CD4 cells. This finding persisted in the patients with sickle cell anemia for up to 3 months after presentation. The lymphocyte responses in both groups probably reflect interactions between adrenergic and steroidal factors.

Acute Disease↗

PubMed1989

CD4/Leu7 and CD8/Leu7 large granular lymphocytosis: comparative studies between NK cells and T cells.

Lymphocytes, co-expressing CD4/Leu7 and CD8/Leu7 markers respectively, taken from two patients having large granular lymphocytosis taking an indolent clinical course have been comparatively studied for function as NK cells and T cells. Both large granular lymphocytes (LGLs) were acid phosphatase positive and showed a beta-glucuronidase reaction in their cytoplasmic granules. Studies on case 1 indicated that the CD4/Leu7 lymphocytosis with LGL morphology takes a benign clinical course with mild neutropenia as well as those of CD8/Leu7 LG lymphocytosis. Both CD4/Leu7 and CD8/Leu7 LGLs behave similarly in their lack of NK activity, and manifest decreased IL-2 production in vitro and show a low IL-2 receptor expression unrelated to their T cell phenotype, but behave differently in influencing the immunoglobulin production in vitro and the ADCC activity, depending on their T cell phenotype and on the expression of Fc receptor, respectively. Furthermore, the altered Fc receptors which were undetectable by the Leul 1 antibody but were still effective for ADCC activity might be present in case 2 LGLs.

Aged↗

PubMed1985

T gamma lymphocytosis is clinically non-progressive but immunologically heterogeneous.

Immunological studies were performed with the expanded T gamma cells of five patients with T gamma lymphocytosis. All patients showed a stable clinical picture with persistent T gamma lymphocytosis and neutropenia, with or without recurrent infections. The expanded T gamma cells in the blood had the T1-3+4-8+11+M1- phenotype, with the exception of one patient whose cells lacked the T8 marker. The expanded T gamma cell population did not proliferate in response to T cell mitogens and did not show immunoregulatory activity on pokeweed mitogen driven immunoglobulin synthesis. In four of the five patients the T gamma cells had killer cell activity against IgG sensitized mouse mastocytoma cells. Taken together, these results and the data from the literature, it is concluded that T gamma lymphocytosis represents a spectrum of T cell expansions clearly distinct from clinically progressive mature T cell neoplasias.

Aged↗

PubMed1988

Spontaneous improvement of juvenile rheumatoid arthritis after T lymphocytosis with suppressor phenotype and function.

Spontaneous improvement of active juvenile rheumatoid arthritis (JRA) occurred after T lymphocytosis in an 8-year-old boy. He had prominent lymphocytosis, the count reaching 59,000/mm3, followed by spontaneous disappearance of fever, arthralgia, lymphadenopathy, hepatomegaly, and C-reactive protein. The serum immunoglobulin levels were gradually decreased. The surface marker analysis, using two color flow cytometry, showed that the lymphocytes were activated suppressor T lymphocytes, expressing CD3, CD8, HLA-DR, and CD8 plus CD11. When studied in vitro with pokeweed mitogen stimulation, the T lymphocytes significantly suppressed the immunoglobulin production by autologous B lymphocytes as compared with the T lymphocytes at remission (p less than 0.01). Based on the widely believed notion that depression of suppressor T lymphocyte functions is one of the important mechanisms underlying systemic JRA, the activated T lymphocytosis with the suppressor phenotype and suppressive function on the immunoglobulin production may have been related to the improvement of active JRA in the patient.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1977

Effect of corticosteroids on exercise-induced lymphocytosis.

Eight subjects ran on a treadmill at 8 miles per hr for 10 min. All developed lymphocytosis with predominant effect on the B cells. This was repeated 5 hr after receiving 60 mg of Prednisone. The lymphocytosis of both T and B cells were suppressed. When this was repeated 2 hr after receiving Prednisone, only lymphocytosis of the T subpopulation was suppressed. It was concluded that corticosteroid administration could suppress entry of lymphocytes into the circulation, with preponderant effect on the T subpopulation.

Adult↗

PubMed1986

T cell receptor gene rearrangements define a monoclonal T cell proliferation in patients with T cell lymphocytosis and cytopenia.

We have used probes from the T cell receptor beta and gamma chain loci to investigate the clonality of T lymphocytes in eight patients with T cell lymphocytosis and cytopenia (TCLC). This syndrome, which is strongly associated with rheumatoid arthritis, is characterized by peripheral blood and bone marrow lymphocytosis and neutropenia, red cell aplasia, or both. By means of T cell monoclonal antibodies and flow cytometry, T lymphocytes from patients with this syndrome have been shown to have characteristic immunologic features. Investigators have disagreed as to whether the syndrome represents a T cell malignancy or a more benign immunologic disorder. DNA from five of five patients with symptomatic "classic" T cell lymphocytosis with cytopenia demonstrated unique rearrangements of the T cell receptor beta chain locus, whereas neither of two patients with atypical features showed rearrangement. In addition, we found evidence for gamma chain rearrangement in those DNAs with clonal beta chain rearrangement. We thus postulate that the classic form of this syndrome is associated with a monoclonal proliferation of T cells. Its potential relationship to T cell chronic lymphocytic leukemia is discussed.

Aged↗

PubMed1987

Lymphocyte surface marker studies in the diagnosis of unexplained lymphocytosis.

Fifty-six patients with unexplained lymphocytosis were investigated with a panel of antibodies to lymphocyte surface antigens. In 23 the distribution of cell surface markers suggested reactive lymphocytosis. The remaining 33 patients showed a distribution of cell surface markers that indicated or suggested a diagnosis of B-cell lymphoproliferative disease. Two illustrative case reports show how such studies performed early in the investigation of unexplained lymphocytosis may permit earlier diagnosis of the underlying mechanism.

Adult↗

PubMed1980

Glucocorticoid receptors in peripheral blood lymphocytes from bovine leukemia virus-infected cows with persistent lymphocytosis.

Bovine leukemia virus-infected cows with persistent lymphocytosis have an expanded population of B-lymphocytes in the peripheral blood that is sensitive to glucocorticoids in vitro and in vivo. We examined peripheral blood lymphocytes from cows with persistent lymphocytosis for the presence of specific glucocorticoid receptors. Steroid binding in intact cells was determined by a whole cell competitive binding assay using [3H]dexamethasone. The binding of the glucocorticoid to receptor was characterized in terms of affinity, specificity, and kinetics of the reaction. We found that peripheral blood lymphocytes from three cows with persistent lymphocytosis had 5000 to 6600 specific glucocorticoid-binding sites/cell. Compared with that reported for human lymphoid cells, glucocorticoid receptors in the bovine lymphocytes were found to have a greater affinity for the steroid with an association rate that was three times faster and a dissociation rate that was less than one-half of the former. We examined the biological half-life of hydrocortisone in the normal cow and found it to be 69.3 min, which is shorter than that reported for other domestic species and humans. The kinetics and affinity of the steroid binding may explain why in vivo glucocorticoid sensitivity was demonstrated in these animals despite the fact that elevated levels of plasma corticoids were not maintained. These results suggest that glucocorticoid sensitivity may be influenced by the nature of the binding reaction between steroid and receptor.

Animals↗

PubMed1993

Persistent polyclonal lymphocytosis in human immunodeficiency virus-1-infected patients.

In this study we describe the clinical, morphologic, immunologic, and genetic features of a chronic peripheral blood lymphocytosis associated with posttraumatic splenectomy in patients with human immunodeficiency virus-1 (HIV-1) infection. Among a series of 2,365 consecutive HIV-1 seropositive cases investigated, eight patients were selected for the presence of more than 4,000 lymphocytes/mm3. All cases were characterized by a lymphocytosis with cytoplasmic azurophilic granules; in three patients the hematologic picture was superimposable with that of lymphoproliferative disease of granular lymphocytes. Phenotypic analysis of lymphocytes showed a prevalent CD3+CD8+ pattern. In vitro evaluations, including the response to mitogens and interleukin-2 and the cytotoxic assays, showed an unimpaired lymphocyte function in the majority of our patients, even in those with advanced stages of the syndrome. The analysis of the configuration of the T-cell receptor (TCR) beta and gamma genes showed a polyclonal pattern of rearrangement. At the mean follow-up time of 45 +/- 8 months, one patient died of overdose when the clinical conditions were stable; all the other patients are alive, although disease progression was documented in two. Our results indicate that a chronic polyclonal lymphocytosis may be associated with HIV-1 infection; this finding seems to be restricted to patients who have undergone splenectomy. The demonstration of a still uncompromised immune system together with a silent clinical course in the patients under study also suggest that splenectomy per se does not favor an aggressive clinical behavior of HIV-1 infection.

CD4-CD8 Ratio↗