Lymphocyte Subsets in Lung Tissues of Non-specific Interstitial Pneumonia and Pulmonary Fibrosis Associated with Collagen Vascular Disorders: Correlation with CD4/CD8 Ratio in Bronchoalveolar Lavage

This study was designed to evaluate the distribution of lymphocyte subsets in lung specimens that were obtained by open-lung biopsy from 8 patients with idiopathic nonspecific interstitial pneumonia/fibrosis (NSIP) and 10 patients with pulmonary fibrosis associated with collagen vascular disorders (PF-CVD). Distributions of B lymphocytes, CD4-positive T lymphocytes, and CD8-positive T lymphocytes were evaluated immunohistochemically and compared with the cell composition in BALF. Correlation between CD4/CD8 ratios in bronchoalveolar lavage fluids (BALF) and CD4/CD8 ratios in lung tissues was also examined. B lymphocytes were mostly restricted in lymphoid follicles. CD4-positive T lymphocytes were observed inside and around lymphoid follicles and in the thick fibrotic wall of reconstructed alveoli with fibrosis. In contrast, CD8-positive T lymphocytes were diffusely distributed, especially in relatively thin alveoli. Correlation was weak between CD4/CD8 ratios in lung tissue and CD4/CD8 ratios in BALF. However, even in patients with very low CD4/CD8 ratios in BALF, many CD4 lymphocytes were observed in lung tissues, suggesting that CD8-positive lymphocytes diffusely distributed in thin alveolar architecture were more easily recovered in BALF than CD4-positive lymphocytes. Therefore, a low CD4/CD8 ratio in BALF may indicate that the alveolar structure was not severely reconstructed by fibrosis. This is the first report that compared lymphocyte subsets in lung tissues and in BALF. Accepted for publication: 14 November 2000     

Which compartments are involved in Philadelphia-chromosome positive chronic myeloid leukaemia? An answer at the single cell level by combining May-Grünwald-Giemsa staining and fluorescence in situ hybridization techniques

Chronic myeloid leukaemia (CML) is believed to represent a stem cell disorder involving all three cell lineages. The typical chromosomal aberration, the Philadelphia chromosome, is the translocation (9;22)(q34;q11). Several studies with cytogenetics, fluorescence in situ hybridization (FISH), or polymerase chain reaction have investigated the presence of the t(9;22) in different cell compartments. However, questions still remain. In six cases of CML we combined the standard May-Grünwald-Giemsa staining with FISH at the single-cell level and were able to demonstrate that not only all maturation stages of granulopoiesis, erythropoiesis, and megakaryocytes, but also plasma cells, eosinophils, basophils and monocytes carried the Philadelphia chromosome in 53–98% of samples. Using immunological identification of single cells we were able to demonstrate that the t(9;22) is detectable in 34% of CD3-positive T lymphocytes, in 32% of CD19-positive B lymphocytes, and in 82% of CD34-positive precursor cells. The results give new insight into the biology of CML and may have implications for future therapeutic strategies.     

高脂血症患者血清补体C3、C4、备解素和白细胞补体调节蛋白CD35、CD55、CD59的表达

目的:探讨高脂血症患者血清补体和外周血白细胞补体调节蛋白的表达及其在动脉粥样硬化中的意义。方法:选高脂血症患者46例(高脂血症组),年龄、性别、体重指数匹配的正常人20例作为正常对照组,用免疫散射比浊法测血清补体C3、C4、备解素(Pf);用流式细胞术测定外周血中性粒细胞、淋巴细胞和单核细胞CD35、CD55、CD59的表达,观察上述指标在高脂血症组中的变化,分析影响因素。结果:高脂血症组血清C3、C4、Pf水平较正常对照组明显升高(P<0.01);补体C3、C4水平与血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDLC)明显正相关(P<0.01),Pf与TC、LDLC正相关(P<0.01)。CD35阳性淋巴细胞、单核细胞、粒细胞百分率较正常对照组升高(P<0.05),CD35阳性淋巴细胞、粒细胞百分率与TG呈正相关(P<0.05～0.01);CD55阳性淋巴细胞平均荧光强度较正常对照组下降(P<0.05);CD59阳性淋巴细胞、单核细胞百分率较正常对照组下降(P<0.05)。结论:高脂血症患者血清补体C3、C4、Pf升高,白细胞补体调节蛋白表达改变,补体及补体调节蛋白的改变与血脂水平相关,表明脂代谢紊乱可影响补体及补体调节蛋白的表达,提示补体及补体调节蛋白可能参与动脉粥样硬化的病理生理过程。     

Telmisartan inhibits CD4-positive lymphocyte migration independent of the angiotensin type 1 receptor via peroxisome proliferator-activated receptor-gamma

Migration of CD4-positive lymphocytes into the vessel wall represents an important step in early atherogenesis. Telmisartan is an angiotensin type 1 receptor (AT1R) blocker with peroxisome proliferator-activated receptor (PPAR)-gamma-activating properties. The present study examined the effect of telmisartan on CD4-positive cell migration and the role of PPARgamma in this context. CD4-positive lymphocytes express both the AT1R and PPARgamma. Stimulation of CD4-positive lymphocytes with stromal cell-derived factor (SDF)-1 leads to a 4.1+/-3.1-fold increase in cell migration. Pretreatment of cells with telmisartan reduces this effect in a concentration-dependent manner to a maximal 1.6+/-0.7-fold induction at 10 mumol/L of telmisartan (P<0.01 compared with SDF-1-treated cells; n=22). Three different PPARgamma activators, rosiglitazone, pioglitazone, and GW1929, had similar effects, whereas eprosartan, a non-PPARgamma-activating AT1R blocker, did not affect chemokine-induced lymphocyte migration. Telmisartan's effect on CD4-positive lymphocyte migration was mediated through an early inhibition of chemokine-induced phosphatidylinositol 3-kinase activity. Downstream, telmisartan inhibited F-actin formation, as well as intercellular adhesion molecule-3 translocation. Transfection of CD4-positive lymphocytes with PPARgamma small interfering RNA abolished telmisartan's effect on migration, whereas blockade of the AT1R had no such effect. Telmisartan inhibits chemokine-induced CD4-positive cell migration independent of the AT1R via PPARgamma. These data provide a novel mechanism to explain how telmisartan modulates lymphocyte activation by its PPARgamma-activating properties.     

T lymphocytes,CD68-positive cells and vascularisation in thyroid carcinomas

Immunohistochemical detection and quantification of CD3-and CD45RO-positive lymphocytes and CD68-positive cells in 75 thyroid carcinomas of follicular cell origin revealed rising levels for these parameters associated with dedifferentiation. A parallel trend towards reduction of vascularisation, determined as CD31-positive blood vessels, with decreasing differentiation became evident, statistically only significant when well-differentiated follicular and anaplastic carcinomas were compared. Positive correlations could be demonstrated between the density of CD68-, CD3-, and CD45RO-positive cells as well as between the density of CD68-, and CD3-, and CD45RO-positive cells and vascularisation. These correlations were expected, as the interaction of CD68-positive cells and T lymphocytes results in the production of angiogenesis factors, ultimately leading to better vascularisation of the tumour. Nevertheless, the tumour cells themselves are variously capable of producing angiogenic substances. The obvious lack of positive correlation between the density of tumour-infiltrating cells determined in this study and vascularisation, despite reduced vascularisation in less differentiated tumours that contained increasing numbers of tumour-infiltrating cells, seems to be due to functional heterogeneity of morphologically similar, tumours.     

Successful treatment of chronic adult T-cell leukemia with ubenimex.

A 38-year-old Japanese man had suffered from trichophyton infection for several years. The white blood cell count was 20,300/mm3, including 54% abnormal lymphocytes with irregularly convoluted nuclei. Adult T-cell leukemia (ATL) was diagnosed based on proliferation of CD4-positive lymphocytes, positive anti-HTLV-I antibody and monoclonal integration of proviral DNA. By 30 mg/day of ubenimex (Bestatin), the abnormal lymphocytes positive for CD4 in the peripheral blood were gradually reduced. Complete remission was maintained for 9 months without any antineoplastic agents. Ubenimex may have suppressed the growth of ATL cells in this patient. Accordingly, ubenimex may prove useful for treating some patients with chronic-type ATL.     

Gain of chromosome 7, which marks the progression from indolent to aggressive follicle centre lymphomas, is restricted to the B-lymphoid cell lineage: a study by FISH in combination with morphology and immunocytochemistry

In a previous fluorescent in situ hybridization (FISH) study of patients with high-grade follicle centre lymphomas (FLCs), we often found additional copies of chromosome 7 in bone marrow (BM) cell nuclei even though obvious malignant tumour cells could not always be morphologically identified in the corresponding cell smears. This raised the question whether the gains of chromosome 7 are really confined to B-lymphoid tumour cells or whether other cell lineages are also of clonal origin. In the present investigation we employed FISH in combination with immunomarkers and morphological studies on BM smears and lymph node imprints from seven patients with high-grade FCLs and diffuse large B-cell lymphomas (DLBCLs). Three out of seven BM samples were found to contain clonal CD20-positive B-lymphoid cells (range 0.4-96% of the cells) and no extra copies of chromosome 7 were detected in the myelomonocytoid or erythroid cells or in the CD3-positive T lymphocytes. All seven patients showed additional copies of chromosome 7 in the lymph nodes and, again, this cytogenetic abnormality was also restricted to the CD20-positive cells (range 0.7-80% of the cells). Thus the present findings confirm that high-grade B-cell lymphomas with or without BM engagement involve the CD20-positive B-lymphoid cells exclusively and not the T lymphocytes, erythroid or myelomonocytoid cell lineages. These findings may indicate that anti-CD20 immunotherapy could be of value in high-grade B-cell lymphomas.     

Flow cytometric analysis of the effect of dithiothreitol on leukocyte surface markers.

Pretreatment with dithiothreitol (DTT) is necessary to dissolve mucus in samples of induced sputum prior to analysis. However, DTT may affect cell surface markers which are essential for lymphocyte subtyping. Therefore, the aim of this study was to evaluate the effect of DTT on an appropriate panel of surface markers. Peripheral blood leukocytes were used because these cells, in contrast to sputum cells, could be obtained without DTT treatment. Peripheral blood from healthy donors was incubated with either DTT according to standard sputum procedures or phosphate-buffered saline (PBS), washed and incubated with fluorochrome-labelled antibodies. After lysis of erythrocytes, analysis was performed using a calibrated flow cytometer. Leukocyte populations were identified by their light scattering properties. For analysis, fluorescence intensity was compared between DTT- and PBS-treated samples. After treatment with DTT, fluorescence intensity was significantly increased in CD16-positive granulocytes; it was reduced in CD2-positive lymphocytes, CD45-positive lymphocytes and CD14-positive monocytes (p < or = 0.001). These changes occurred in all samples. The fluorescence intensity of CD3-, CD4-, CD8-, CD19-, CD56- and histocompatibility leukocyte antigen DR-positive lymphocytes was not altered by DTT. However, there were statistically significant (p<0.001), although small, changes in the percentages of leukocytes. The present data demonstrate that, although dithiothreitol as used in sputum analysis affects some surface markers of peripheral blood leukocytes, comparability between samples concerning lymphocyte surface markers is preserved. Therefore, it is suggested that treatment of sputum samples with dithiothreitol does not invalidate the immunocytochemical analysis of lymphocytes.     

Flow cytometric study of lymphocyte subsets in patients at different stages of colorectal carcinoma

PURPOSE: The evaluation of lymphocyte subsets by using monoclonal antibodies in neoplastic patients has provided different results, partly in relation to the stage of the disease. Therefore, as a preliminary study of cancer patients treated with immunomodulating drugs, an analysis of lymphocyte subsets was performed in colorectal carcinoma patients. METHODS: In this study, a flow cytometric evaluation of lymphocyte subsets was performed in 33 patients affected by colorectal carcinoma, with or without metastases. RESULTS: A significant reduction of hemoglobin concentrations and hematocrit was observed in all of these subjects, associated with an evident increase of white blood cells, platelets, and HLA DR-positive T lymphocytes, whereas CD 3-CD 4-positive and CD 20-positive lymphocyte concentrations were decreased. Subjects without metastases showed an evident decrease of hemoglobin concentrations and an increase of white blood cells, platelets and CD 3-HLA DR-positive lymphocytes, while patients with disseminated disease also had reduced mean values of hematocrit, red blood cells, CD 3-CD 4-positive, and CD 20-positive lymphocytes. CONCLUSIONS: The main differences between colorectal carcinoma patients with or without metastases were represented by a decrease of red blood cells, CD 3-CD 4-positive, and CD 20-positive lymphocyte concentrations in the latter group.     

CD69 expression on lymphocytes and interleukin-15 levels in synovial fluids from different inflammatory arthropathies

OBJECTIVE: The aim was to study a possible relationship between CD69 expression on lymphocytes and interleukin-15 (IL-15) levels in synovial fluid (SF) from patients with different inflammatory arthropathies. METHODS: CD69 expression was assessed by two-color flow cytometry on different subsets of synovial fluid lymphocytes (SFL) obtained from patients with diagnoses of rheumatoid arthritis (RA), seronegative spondyloarthropathy (SSd), and crystal-associated arthritis (CAA). The IL-15 levels in synovial fluid supernatants were measured by enzyme-linked immunoassay (ELISA). RESULTS: No significant differences between the three groups of arthropathies were observed in the distribution of synovial fluid lymphocyte subsets. CD69-positive SFL were mainly CD3-, CD45RO-, and CCR5-positive cells. Although no significant differences in the percentage of CD69-positive lymphocytes were observed between the three groups of patients, the highest level of CD69 expression on lymphocytes was observed in RA patients (mean fluorescence intensity 37.9 +/- 5.2 compared to 17.5 +/- 3.3 in SSd and 12.4 +/- 2.6 in CAA, P = 0.007 and P < 0.001, respectively). In addition, the expression of CD69 on SFL from RA correlated with their respective IL-15 levels measured in SF supernatants. CONCLUSION: Our data provide in vivo evidence of the putative role that IL-15 can play in the high expression of CD69 on SFL from RA patients.     

Marked up-regulation of T lymphocytes and expression of interleukin-9 in bronchial biopsies from patients With chronic bronchitis with obstruction

STUDY OBJECTIVE: To examine the differences in the inflammatory cell and cytokine profile between patients with chronic bronchitis (CB) with and without airway obstruction compared to control subjects. DESIGN: We used bronchial biopsy samples from the patients and control subjects and analyzed them for the presence of CD3 T cells, CD68, major basic protein (MBP), elastase, and tryptase, as well as expression of messenger RNA (mRNA) coding for interleukin (IL)-4, IL-5, interferon (IFN)-gamma, IL-9, eotaxin, and IFN-gamma-inducible protein (IP)-10. The techniques of immunocytochemistry and in situ hybridization were used. Results were expressed as the number of immunoreactive and mRNA-positive cells per field. RESULTS: Increased number of elastase, CD68, and MBP-positive cells (n = 9, p < 0.01) was demonstrated in both groups of patients with CB compared to control subjects. In patients with CB and obstruction, the number of elastase, CD68, and the number of CD3-positive cells was significantly increased compared to patients with CB without obstruction (n = 9, p < 0.01). IFN-gamma mRNA expression was increased in both groups of patients with CB compared to control subjects (n = 9, p < 0.01). IL-9 mRNA was significantly increased only in patients with CB and obstruction (n = 9, p < 0.01). Co-localization studies demonstrated > 80% of all IL-9-positive cells to be CD3-positive T cells. IP-10 mRNA was significantly increased in both groups of patients with CB compared to control subjects (n = 9, p < 0.01). CONCLUSIONS: These results indicate a differential expression of inflammatory markers and cytokine mRNA in patients with obstructive CB. Increased presence of T lymphocytes and up-regulation of IL-9 and IP-10 mRNA expression in the bronchial biopsy samples may contribute to the airway obstruction in these patients.     

Lymphoproliferative disease of granular lymphocytes with T-cell receptor gamma delta-positive phenotype: restricted usage of T-cell receptor gamma and delta subunit genes

Lymphoproliferative disease of granular lymphocytes (LDGL) is characterized by more than 0.5 x 109/L of proliferating granular lymphocytes in the peripheral blood. Because of its rarity, the characteristics of LDGL with T-cell receptor (TCR) gammadelta phenotype (gammadeltaT-LDGL) have not yet been identified. This report describes the clinical, hematological, and immunological findings of four patients with this disease. In two cases, the clinical course was indolent and the other two patients required various therapies. The cells had a common immunophenotype: CD3+, CD4-, CD16+, CD56-, CD57-, CD122-, TCR-gammadelta+, and three were CD8-positive. The immunopurified TCR-gammadelta cells from the patients expressed only Vgamma9 and Vdelta1. Spectratyping and sequencing showed mono- or oligoclonality for TCRgamma and TCRdelta subunit genes. Soluble Fas ligand in sera was significantly elevated in all patients. These findings suggest that gammadeltaT-LDGL qualifies as a distinct disease entity.     

Effect of long-term infection with nef-defective attenuated HIV type 1 on CD4+ and CD8+ T lymphocytes: increased CD45RO+CD4+ T lymphocytes and limited activation of CD8+ T lymphocytes

Members of the Sydney Blood Bank Cohort (SBBC) have been infected with an attenuated strain of HIV-1 with a natural nef/LTR mutation and have maintained relatively stable CD4+ T lymphocyte counts for 14-18 years. Flow cytometric analysis was used to examine the phenotype of CD4+ and CD8+ T lymphocytes in these subjects, including the immunologically important naive (CD45RA+CD62L+), primed (CD45RO+), and activated (CD38+HLA-DR+ and CD28-) subsets. The median values were compared between the SBBC and control groups, comprising age-, sex-, and transfusion-matched HIV-1-uninfected subjects; transfusion-acquired HIV-1-positive LTNPs; and sexually acquired HIV-1-positive LTNPs. Members of the SBBC not only had normal levels of naive CD4+ and CD8+ T lymphocytes, but had primed CD45RO+ CD4+ T lymphocytes at or above normal levels. Furthermore, these primed cells expressed markers suggesting recent exposure to specific antigen. SBBC members exhibited variable activation of CD8+ T lymphocytes. In particular, SBBC members with undetectable plasma HIV-1 RNA had normal levels of activated CD8+ T lymphocytes. Therefore, the result of long-term infection with natural nef/LTR mutant HIV-1 in these subjects suggests a decreased cytopathic effect of attenuated HIV-1 on susceptible activated CD4+ T lymphocyte subsets in vivo, and minimal activation of CD8+ T lymphocytes.     

Activated interstitial and intraepithelial thyroid lymphocytes in autoimmune thyroid disease

This study has further characterised the thyroid lymphocytic infiltrate in Graves' disease and Hashimoto's thyroiditis. Two population of lymphocytes were identified. The interstitial population occurred as a diffuse and a focal infiltrate; most cells were CD3-positive (T cells) and in 4 of 6 glands CD8 (suppressor-cytotoxic)-positive T cells predominated. The intraepithelial population was CD3-negative, CD8-positive. Both populations also contained a few NK (Leu 11b positive cells) in some glands. Many of the lymphocytes in both populations stained with UCHL1 and RFT2 suggesting that these are primed and activated cells, borne out by staining for transferrin receptor expression. Although thyroid follicular cells were Ia-positive, macrophages and dendritic cells were found in all cases, so that a role for antigen-presentation by all three potential candidates in autoimmune thyroiditis is possible.     

Graves' disease with splenomegaly and pancytopenia, mimicking B-cell lymphoproliferative disease

A 48-year-old woman was referred to our hospital because of fever and general fatigue. Peripheral blood analysis showed a hemoglobin level of 82 g/l, a white blood cell count of 1.95 x 10(9)/l and a platelet count of 80 x 10(9)/l. There were 9% CD5-positive B-cells in peripheral blood and 35% CD10-positive B-cells in bone marrow. The patient had a high serum soluble interleukin-2 receptor (SIL-2R) level of 5,185 U/ml and splenomegaly. Lymphoproliferative disease was suspected, however monoclonal rearranged band of immunoglobulin heavy chain was not detected. She also showed hyperthyroidism, Graves' disease and then treatment with thiamazole started. However, the treatment was stopped because of agranulocytosis and she received subtotal thyroidectomy. After treatment for hyperthyroidism, serum SIL-2R level decreased to 504 U/ml and pancytopenia gradually improved. Fifteen months postoperatively, the percentage of CD5-positive B-cells in peripheral blood and CD10-positive B-cells in bone marrow decreased to 8% and 2%, respectively. This clinical course suggests that polyclonal B-cell proliferation was caused by hyperthyroidism.     

Direct recognition and lysis of leukemia cells by WT1-specific CD4+ T lymphocytes in an HLA class II-restricted manner

Wilms tumor gene 1 product (WT1) has been recognized as an attractive target antigen of immunotherapy for various malignancies including leukemia. Because tumor-associated antigen-specific CD4+ T lymphocytes undoubtedly play an important role in the induction of an antitumor immune response, we attempted to generate WT1-specific CD4+ T lymphocytes in vitro and examined their antileukemia functions. A CD4+ T-cell line, designated NIK-1, which proliferated and produced Th1 cytokines specifically in response to stimulation with the WT1-derived peptide, WT1(337-347) LSHLQMHSRKH, in an HLA-DP5-restricted manner was established. NIK-1 exhibited cytotoxicity against HLA-DP5-positive, WT1-expressing leukemia cells but did not lyse HLA-DP5-negative, WT1-expressing leukemia cells or HLA-DP5-positive, WT1-negative cells. NIK-1 did not inhibit colony formation by normal bone marrow cells of HLA-DP5-positive individuals. This is the first report to describe WT1-specific and HLA class II-restricted CD4+ T lymphocytes possessing direct cytotoxic activity against leukemia cells.     

肝内IFN-γ及其分泌细胞在乙型慢加急性肝衰竭发病机制中的作用

目的通过研究肝内促炎细胞因子IFN-γ的表达及IFN-γ的分泌细胞——T淋巴细胞的数量,以明确二者在乙型慢加急性肝衰竭（acute—on—chronic liver failure,ACLF）发病机制中的作用。方法采用免疫组化方法,分析乙型ACLF患者、慢性乙型肝炎（乙肝）患者及正常对照组肝内IFN-γ的原位表达以及其分泌细胞CD4^＋T淋巴细胞与CD8^＋T淋巴细胞的数量。结果①乙型ACLF患者IFN-γ阳性分泌细胞数均明显高于慢性乙肝患者及正常对照组,差异有统计学意义（P均〈0．001）,慢性乙肝患者IFN-γ阳性分泌细胞数明显高于正常对照组,差异有统计学意义（P〈0．001）;②乙型ACLF患者肝内CD4^＋和CD8^＋T淋巴细胞数量较慢性乙肝及正常对照组明显增加（P均〈0．001）,慢性乙肝患者肝内CD4^＋和CD8^＋T淋巴细胞数量较正常对照组明显增加（P均〈0．001）;③肝内IFN-γ阳性分泌细胞数量与CD4＋T淋巴细胞和CD8^＋T淋巴细胞数量均具有明显的相关性（r=-0．896和0．885,P均〈0．001）。结论乙型ACLF患者肝内CD4^＋T淋巴细胞、CD8^＋T淋巴细胞数量的增加,其分泌的IFN-γ的增加可能参与了ACLF的发病过程。     

DNA synthesis in CD4- and CD8-positive cells in synovial fluid of patients with reactive and rheumatoid arthritis

Summary The occurrence of MHC class I antigens and microbial antigens derived from the triggering infection of the diseased joints in reactive arthritis (ReA) seems to set the stage for local immune activation. In this report activated lymphocytes are demonstrated by using an avidin-biotin-peroxidase complex (ABC) method combined with autoradiography that identifies DNA synthesis and, thus, activation. Most of the activated T lymphocytes in reactive arthritis were found to belogn to the CD8 suppressor/cytotoxic T-lymphocyte subset. In striking contrast, the majority of the activated T lymphocytes detected in rheumatoid arthritis (RA) synovial fluid belonged to the CD4 helper/inducer subset. These findings agree well with the assumption that CD8-positive cells identify the foreign antigen in the context of class I antigens, whereas CD4-positive cells are found to be associated with the recognition of MHC locus II coded HLA antigens.     

CD56-positive peripheral T-cell lymphoma primarily presenting with tonsillar swelling

A 51-year-old woman was admitted to our hospital with tonsillar swelling. After tonsillectomy was performed, she was diagnosed as having CD56-positive T-cell lymphoma, mainly composed of small and medium-sized atypical cells. An immunohistochemical study showed that the malignant lymphocytes were positive for CD3, CD8, CD56, TIA-1 and granzyme B, while negative for CD20, CD5 and CD10. Flowcytometry demonstrated the lymphocytes were positive for CD56. Southern blot analysis revealed a rearrangement of the T-cell receptor gamma chain. The disease stage by Ann Arbor staging classification was II B. We provided MCEC therapy followed by autologous peripheral blood stem cell transplantation, and complete remission (CR) was achieved. Two months after CR, however, the patient relapsed with peritonitis due to perforation of an ileal tumor, and died of sepsis. It is rare for CD56-positive T-cell lymphoma to occur primarily in the tonsils. Because small bowel ulcers were revealed during the course of induction chemotherapy, we report a valuable case in which suspected CD56-positive enteropathy-type T-cell lymphoma (ETL) occurred primarily in the tonsils.     

Helper and suppressor T-cell function in HIV-infected hemophilia patients

T-lymphocyte helper and suppressor functions were assessed in 61 hemophilia patients. Twenty one patients were HIV-negative (Group 1), 27 were HIV-positive without having AIDS-related complex (ARC)/AIDS (Group 2), and 13 had ARC/AIDS (Group 3). T, CD4-positive, or CD8- positive T lymphocytes were cocultured with B lymphocytes and pokeweed mitogen for 6 days and immunoglobulin producing cells were assessed in a reverse hemolytic plaque assay. In HIV-infected patients, T cells as well as the CD4-positive T cell subset exhibited reduced helper (P less than .01, Group 2; P less than .0005, Group 3) and elevated suppressor activity (P less than .02, Group 2; P less than .005, Group 3), whereas no significant difference was found between HIV-negative patients and controls. The number of CD4-positive cells was not correlated with CD4 cell function. CD4-positive cells showed no helper activity (less than 10% of control T cells) in 8/11 (73%), but an excessive suppressor activity (greater than 80% suppression of plaque formation) in 6/11 (55%) Group 3 patients. Our results show that defective helper and elevated suppressor functions of T cells in HIV-infected patients are caused not only by a change in the CD4/CD8 cell counts but also by functional abnormalities of the CD4-positive T-cell subset. These abnormal helper and suppressor functions may play a role in the development of the immunodeficiency state of AIDS patients.