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The influence of thalidomide therapy on cytokine secretion, immunophenotype, BCL-2 expression and microvessel density in patients with resistant or relapsed multiple myeloma.

Thalidomide (THAL) is currently used as a novel drug in patients with chemotherapy resistant or relapsed multiple myeloma. THAL antitumor activity seems to be very complex, however the precise mechanisms of its action are still not fully understood. The aim of this study was to assess some of possible mechanisms of THAL action both in in vivo analysis of immune cells phenotype and in in vitro cultures with THAL. The study involved 30 patients with relapsed or chemotherapy refractory multiple myeloma who were qualified to THAL treatment. We assessed immunophenotype of malignant plasma cells and T lymphocytes in both peripheral blood (PB) and bone marrow (BM) samples taken before and after 4 and 8 weeks of THAL treatment. Before therapy cytokine secretion (VEGF, HGF, bFGF, TNF, IL-6 an sIL-6R) and Bcl-2 expression in PB and BM cell cultures with THAL were analyzed. We used flow cytometry technique and ELISA method. The clinical response to therapy was assessed after 4 and 8 weeks of treatment. We also investigated microvessel density (MVD) in bone marrow samples before the THAL treatment and after 6 months of therapy in the group of responding patients. In cell cultures with THAL we detected statistically significant lowering of analyzed cytokines concentration and the decrease in Bcl-2 expression by malignant plasma cells in BM and CD8(+) T lymphocytes in BM and PB. In the group of patients responding to therapy we observed the decrease in the number of myeloma cells and significant increase of CD4(+) and CD8(+) cells in both PB and BM samples. There was statistically significant increase of CD3(+)/CD69(+) cells in the course of therapy, while the percentage of CD3+/HLA-DR(+) cells was significantly lower after 8 weeks of therapy. We also detected lowering of MVD after THAL therapy in responders group. The obtained results demonstrate that THAL efficacy in MM is multidirected and included such mechanisms like down-regulation of proangiogenic cytokines, that could lead to lowering of MVD, induction of apoptosis and influence on malignant cells and T lymphocytes immunophenotype.

Administration, Oral↗

Immunophenotypically heterogeneous acute T-lymphoblastic leukemia has invariable immunogenotype: analysis of two cases.

Two patients with acute T-lymphoblastic leukemia showed heterogeneous expression of some immunophenotypic cell markers. Cell sorting was used to separate two CD34/CD117/TCRgammadelta and CD34/CD117/TCRgammadelta cell populations. The sorted TCRgammadelta population had more cells in S phase than the TCRgammadelta population. PCR analysis revealed identical TCR gene rearrangements in both populations. At relapse of one of the patients, only CD117, CD34, TCRgammadelta cells remained. The authors assume the presence of two immunophenotypically different cell subsets in different maturation stages at diagnosis.

Adolescent↗

[Solitary plasmacytoma: a clinicopathologic and immunophenotypic analysis of 43 cases].

OBJECTIVE: To investigate the clinicopathologic and immunophenotypic features of solitary plasmacytoma and discuss the diagnosis and differential diagnosis of the tumor. METHODS: Clinicopathological study and follow up study were made on 43 cases of solitary plasmacytoma, including 24 cases of extramedullary plasmacytoma (EMP) and 19 cases of solitary plasmacytoma of bone (SPB). Immunohistochemical staining was performed by SP method using antibodies CD20, CD79a, PC, Ig kappa, Ig lamda, IgA, IgD, IgE, IgG and IgM. RESULTS: Rgarding EMP, the male/female ratio is 2.5 to 1, the age ranges from 3 to 70 years (mean 49). Clinically, the neoplasms of 22 cases were located in nasal cavity or nasosinus, 2 cases were located in lung and tonsil respectively. Rgarding SPB, the male/female ratio is 1:1, the age ranges from 36 to 72 years (mean 53). Clinically, the neoplasms of 8 cases were located in vertebrae, 3 cases in pelvis, 6 cases in clavicle, rib and femur respectively, 2 case in radius and tibia respectively. Histopathological examination revealed tumor cells diffuse infiltration with necrosis and ulceration; the well-differentiated tumor cells were similar to the normal plasmacyte in shape; the poorly-differentiated tumor resembled centroblasts; there were a few interstitial tissues with plenty of vessels or formation of blood lakes; and there was deposition of amyloid materials. Immunophenotypic analysis showed that all tumor cells were positive for CD79a and negative for CD20; that plasma cell marker (VS38C) was expressed in 41 cases; that light chain restriction was detected in all 43 cases( 31 for lamda and 12 for kappa), and that heavy chain expression was detected in 39 for IgG, 1 for IgA, 2 for both IgG and IgM, and 1 for IgA/IgG. CONCLUSION: The special histopathology in this group of solitary plasmacytomas is presented. The well-differentiated tumors should be distinguished from reactive plasmacytosis and MALT. And, when poorly-differentiated solitary plasmacytomas were tentatively diagnosed, large cell lymphoma, melanoma and poorly differentiated carcinoma should be considered in differential diagnosis.

Adolescent↗

[Four-color flow cytometric immunophenotypic features of blasts in myelodysplastic syndromes].

This study was aimed at exploring the immunophenotypic features of blasts in patients with myelodysplastic syndromes (MDS). Four-color flow cytometry using conventional and secondary gating strategies was used to immunophenotype blasts and the CD34 positive cells in bone marrow nucleated cells of 29 patients with MDS. The results showed: (1) with progression of MDS from RA/RAS, RAEB to RAEB-T, the proportion of CD34(+) cells were gradually increased from 8.0%, 46.4% to 76.8% (P < 0.05); (2) using CD45 vs SSC gating strategy, with the transformation of RA/RAS, RAEB to RAEB-T, the expression of HLA-DR, CD13, CD33, CD117 were also gradually increased (P < 0.05), and the expression of CD15 was gradually decreased (P < 0.05); (3) using CD45 vs CD34 gating strategy, the expression of HLA-DR, CD13, CD33, CD117 on blasts were higher by secondary gating method than those by conventional gating (P < 0.05). However, there were no significant difference (P > 0.05) in the expression of above-mentioned antigens on CD34(+) cells among different MDS subtypes. It is concluded that conventional gating method can reflect MDS progression from RA/RAS, RAEB to RAEB-T, and secondary gating strategy may accurately reflect the biological features of blasts in MDS. Abnormal expression of CD34 is related to the immaturity level and heterogeneity of blast cells, which is beneficial to the diagnosis of clinically suspected MDS incapable of diagnosing with morphology and cytogenetics.

Adult↗

Minimal residual disease testing of acute leukemia by flow cytometry immunophenotyping: a retrospective comparison of detection rates with flow cytometry DNA ploidy or FISH-based methods.

The detection and quantification of minimal residual leukemia (MRD) has importance for monitoring continued disease response and detection of early relapse. We retrospectively compared MRD detection rates and percentages of residual leukemia by flow cytometry immunophenotyping (FCIP) with results obtained by either flow cytometry DNA (FCDNA) ploidy (n = 14) and/or fluorescent in situ hybridization (FISH) (n = 33) testing for cases with 1.5% or less residual leukemia. A total of 42 paired results were obtained from 20 pediatric patients, including 16 with B lineage acute lymphocytic leukemia and 4 patients with acute myeloid leukemia during the course of induction and/or relapse. Eighty-one percent of the results were concordant (20 negative and 14 positive). There was reasonable correlation coefficients for quantity of residual disease by FCIP and FCDNA ploidy, and poor correlation coefficients for levels of residual disease between FCIP- and FISH-based results. FCIP MRD sensitivity and specificity was 78% and 83%, respectively. Factors contributing to the 19% discordant rate include low sensitivity of the DNA-based methods as applied and antigenic modulation of immunophenotype during the course of treatment. There is a reasonable agreement between the FCIP and FCDNA or FISH methods for detecting and quantifying MRD. However, the methods are viewed as complementary with their own inherent limitations.

Acute Disease↗

Germ line insertions of moloney murine leukemia virus in the TLL mouse causes site-specific differences in lymphoma/leukemia frequency and tumor immunophenotype.

BACKGROUND: Moloney murine leukemia virus (Mo-MLV) has proven valuable for studies of the pathogenesis of malignant lymphoma. Inoculation of newborn mice induces T cell lymphoma with 100% incidence. The TLL (T cell lymphoma/leukemia)-strain was previously established and was shown to spontaneously develop T cell lymphoma at high frequency. MATERIALS AND METHODS: Differential screening of cDNA libraries was performed to discover an involvement of Mo-MLV and genomic sequencing was used to identify the chromosomal position of Mo-ML V proviral integration sites. Immunophenotypes of the tumors were established by flow cytometty. Disease frequency curves were created according to the Kaplan-Meier method. RESULTS: Two independent Mo-MLV germ line integrations were characterized on chromosomes 2 and 14, giving rise to two substrains of mice denoted TLL-2 and TLL-14. The chromosomal position of the integrated provirus affected the frequency of disease, as well as the immunophenotype of the tumors. CONCLUSION: The data suggest that factors influencing the transcriptional activity of the chromosomal regions, leading to differences in proviral expression, could underlie the observed difference in tumor frequency.

Animals↗

[Growth, immunophenotype and interleukin-6 level of bone marrow stromal cells in patients with multiple myeloma and acute leukemia].

The aim of this study was to investigate the growth, immunophenotype and interleukin-6 (IL-6) level of bone marrow stromal cells (BMSC) in patients with acute leukemia (AL) and multiple myeloma (MM). BMSC was cultured by wall-adhesion method and the growth of BMSC was observed. The immunophenotype and cell cycle of BMSC were detected by flow cytometry. The level of interleukin 6 (IL-6) in BMSC culture system was detected by ELISA. The results showed that the primary (17.3 +/- 7.8 days) and continuous (10.3 +/- 3.5 days) growth cycle of BMSC in patients with AL were significantly shorter than those in patients with MM (26.5 +/- 6.3 and 16.5 +/- 4.1 days respectively), and shorter than those in normal controls (25.8 +/- 6.3 and 17.5 +/- 2.4 days) respectively. Similarly, S + G2% (17.4 +/- 3.6%) of BMSC in patients with AL was significantly higher than those in patients with MM (8.5 +/- 2.2%) and in normal controls (8.9 +/- 2.3%). All of the three groups showed positive antigen expressions with CD29 and CD44 were 100%, while CD138, CD34, CD54, CD56 positive were not expressed and CD106 was partially expressed positive. The supernatant IL-6 level of BMSC system in MM patients (1288.5 +/- 736.7 pg/ml) was significantly higher than those in AL patients (859.3 +/- 203.1 pg/ml) and normal controls (850.9 +/- 129.5 pg/ml). It is concluded that the growth, S + G2% of cell cycle and IL-6 level of BMSC in patients with MM, AL and normal control are significantly different, whereas the antigen expressions are similar.

Acute Disease↗

[Immunophenotypic characteristics of children with acute lymphoblastic leukemia carrying TEL-AML1 fusion gene].

To investigate the immunological and other clinical characteristics in TEL/AML1+ childhood B-acute lymphoblastic leukemia (B-ALL), immunophenotyping was performed with three-color flow cytometry, and the expression of TEL-AML1 fusion gene was detected with nested RT-PCR. Diagnosis was made according to FAB and MIC criteria. The results showed that (1) among 119 children with B-ALL, 22 (18.5%) were TEL-AML1 positive and classified as L2 morphological subtype. In TEL-AML1+ group, positive rate and score of PAS, which were 65% and 121 respectively, were all higher than that of TEL-AML1- group (P < 0.05); (2) compared with TEL-AML1- group, no significant difference was found in age, gender, white cell count and blasts count in peripheral blood of TEL-AML1+; (3) in TEL-AML1+ group, 21 out of 22 (95.5%) were common ALL, as compared with TEL-AML1- group, the positive rate of CD13 was higher (59.1%, 13/22) and the positive rate of CD20 was lower (22.7%, 5/22) than that in TEL-AML1- group, respectively (P < 0.05), and the mean fluorescence index of CD10 and HLA-DR significantly increased to 92.80 and 53.61, respectively (P < 0.05). It is concluded that TEL-AML1 rearrangement is a frequent molecular abnormality in childhood ALL. Leukemic blasts with this anomaly have special immunophenotypic characteristics. These characteristics may be useful in detection of minimal residual leukemia.

Antigens, CD20↗

Immunophenotypical profiles of salivary gland tumours: a new evidence for their histogenetic origin.

The histogenetic origin of salivary gland tumours is not clear. In normal tissues smooth muscle actin (SMA) is expressed in myoepithelial cells, CK14 immunoreactivity is seen in myoepithelial and basal cells and CK10 in keratinized squamous epithelium. In this study, we examine the immunophenotypic properties of salivary gland tumours in order to obtain further insight into their histogenesis. 30 cases of salivary gland tumours (18 pleomorphic adenomas, 8 Warthin's tumours, 2 basal cell adenomas, 2 acinic cell carcinomas) were included in our study. Cytokeratin (CK) 10, CKI4, CKI7, CK18, CK 19, and smooth muscle actin (SMA) immunostains were applied to the sections. Immunoreactivities were detected and the statistical significance was evaluated by chi square test. SMA was not detected in Warthin's tumour (p < 0.0001). CK14 was found in all tumours except acinic cell carcinomas (p < 0.0001). CK10 immunoreactivity was observed in 5 Warthin's tumour. In conclusion, pleomorphic adenomas and basal cells adenomas originate from stem cells. Immunophenotypic profile of Warthin's tumour is suggestive of an embryological remnant origin.

Actins↗

Immunophenotyping of amelanotic melanoma. A case report.

Amelanotic malignant melanoma (AMM) is a subtype of cutaneous melanoma with little or no pigment upon visual inspection. The lack of pigmentation is the reason for late diagnosis of lesions and a poor prognosis. We report a case of a 55-year-old female with an AMM diagnosed by immunophenotyping. Monoclonal antibodies S-100, HMB-45, and antibodies to cytokeratin were used. Our patient underwent a wide local excision (a 2 cm wide margin) 2 years ago. So far there are no signs of a recurrence. In doubtful cases, immunophenotyping with monoclonal antibodies HMB-45 and S-100 is important for confirming the correct diagnosis of AMM.

Antibodies↗

Reevaluation of the periodic acid-Schiff stain in acute leukemia with immunophenotypic analyses.

To determine the sensitivity and specificity of the periodic acid-Schiff (PAS) stain in the diagnosis of acute leukemia in light of the finer characterization of this disorder now available through immunophenotyping, we examined the blasts from 51 patients with newly diagnosed acute leukemia by morphological, cytochemical, and immunophenotypic analyses. The 51 patients represented every new case of acute leukemia subjected to cytochemical stains and flow cytometry between July 1987 and February 1989. By cell-surface marker analysis, 29 exhibited lymphocytic lineage, while 21 were myelocytic. One was mixed lineage. The PAS positivity, defined by the presence of blocks or coarse granules in 5% or more of the blasts, was found in 15 of 29 lymphoblastic leukemias and in four of the myeloblastic leukemias. However, PAS-positive lymphoblastic leukemias were negative with the other cytochemical stains: myeloperoxidase, Sudan black B, and alpha-naphthyl butyrate esterase. The PAS-positive myeloblastic leukemias were positive with at least one other stain. Three cases of myeloblastic leukemia exhibited greater than 10% PAS-positive blasts, with all three being acute monoblastic leukemia. Thus, the sensitivity and specificity of the PAS stain alone for lymphoblastic leukemia was 52% (15 true positives of 29) and 81% (four false positives), respectively. The sensitivity of a cytochemical-staining combination of PAS positivity and myeloperoxidase, Sudan black B, and alpha-naphthyl butyrate esterase negativity in defining cases of lymphoblastic leukemia remained at 52%; however, the specificity of this combination for lymphoblastic leukemia was 100% (no false positives). Thus, a positive PAS stain, in combination with negative myeloperoxidase, Sudan black B, and alpha-naphthyl butyrate esterase stains, continues to have a diagnostic role in the distinction between lymphoblastic and myeloblastic leukemia, and greater immunologic sophistication serves to support this position.

Acute Disease↗

[Leukemia-associated immunophenotypes in 415 childhood and adult patients with B lineage acute lymphoblastic leukemia by multiparametric flow cytometry analysis].

To evaluate the significance of FCM in minimal residual disease (MRD) detection, the immunophenotyping and leukemia-associated immunophenotypes (LAIP) of leukemia cells from 273 adult and 142 childhood patients with B lineage acute lymphoblastic leukemia (B-ALL) were detected by four to six antibody combinations of 4-color CD45/SSC gating multiparametric flow cytometry (FCM). The results showed that the B-ALL patients could be classified into 4 subtypes based on different expression CD34 and CD10: subtype I (CD34(+)/CD10(-)), subtype II (CD34(+)/CD10(+)), subtype III (CD34(-)/CD10(+)), subtype IV (CD34(-)/CD10(-)). The LAIP was observed in 100% and 92% patients of subtype I and subtype II, respectively, whereas only 79.2% in subtype III. The incidence of LAIP in total B-ALL cases was 90% by using the antibodies detected in this investigation. There was no significantce different for incidence of LAIP between adult and pediatric patients. LAIP was observed in 77.6% of patients by labeling only CD34/CD10/CD19/CD45 4-color antibody combination. It is concluded that in 90% of childhood and adult B-ALL patients LAIP can be found, which suits MRD detection by multiparameter flow cytometry.

Adolescent↗

Role of FAB classification of acute leukemias in era of immunophenotyping.

French-American-British classification for leukemias had been widely accepted due to its objectiveness and good reproducibility. WHO classification of leukemias was formulated in 1997 with a purpose of further enhancing the objectivity. However, the requirement of cytogenetics and immunophenotyping makes it difficult for many countries like India to put WHO classification in routine use. This study was carried to know the effectiveness of FAB classification in an era of technical advancement. A retrospective analysis of all acute leukemias over a period of 2 years was done. Out of total of 469 cases of acute leukemias, 193 were diagnosed as Acute Lymphoblastic Leukemia (ALL), 200 as Acute Myeloid Leukemia (AML), and 76 cases diagnosed as Acute Leukemia, cytochemically undifferentiated. Hence, only 16% of all leukemias remained unclassifiable. Subclassification of AML cases revealed a much higher percentage of AML-M3, as compared to western literature. In conclusion, FAB classification, based on morphology and simple cytochemical stains, remains effective enough, although cytogenetics and immunophenotyping can add to diagnostic accuracy in some cases.

Acute Disease↗

Immunophenotype of sporadic and familial adenomatous polyposis associated fundic gland polyps: a mucin and MIB1 study.

BACKGROUND: Fundic Gland Polyps (FGPs) are small sessile (2-5 mm) usually multiple polyps arising in the gastric, acid-secreting mucosa, described both in a sporadic form, prevalently in middle aged females, and associated with familial adenomatosis coli (FAP)-Gardner's syndrome and their attenuated variants (syndromic form). AIMS: We performed an immunohistochemical study on 5 syndromic (4 cases without and 1 case with dysplasia) and 28 sporadic FGPs, using monoclonal antibodies (MoAbs) against normal epitopes of fundic mucosa (Ck20, the surface gastric mucin M1, EMA, ChA), H. pylori and HLA-DR(Ia) antigens, CEA and mucin epitopes, and the Ki67 (MIB1) proliferation antigen, in order to establish the immunophenotype of FGPs; find any possible differences between sporadic and syndromic polyps. RESULTS: Ck20 and M1 were positive on surface and foveolar epithelium of controls, whereas sporadic and syndromic FGPs showed an enhanced deep positivity below foveolar necks ("foveolar metaplasia"); EMA was strongly positive on parietal cells, highlighting intracytoplasmic canaliculi. Chromogranin-positive cells in FGPs were alike controls, except for a sporadic case with micronodular hyperplasia. Ck7, as expected, was negative in controls, whereas the 5 syndromic FGPs and 25 of 28 sporadic FGPs showed a diffuse superficial and deep expression. H. pylori anti-serum gave negative results on all cases, and only 3 sporadic FGPs showed epithelial expression of HLA-DR(Ia). Syndromic FGPs were CEA negative, whereas 32% of sporadic FGPs expressed it. FGPs showed a neoexpression of the mucin oncofetal epitopes syalil-Tn (3/5 syndromic, 82% sporadic) CA19.9 and CA50 (4/5 syndromic, 14% sporadic). MIB1-labelling index of surface (30.5%) and deep (37.1%) compartments of the 4 syndromic FGPs without dysplasia was enhanced, with high statistical significance (p < 0.0001) both in comparison to controls (16.9% superficial stain only) and sporadic FGPs (15.8% surface, 19.5% deep labeling indexes). Moreover, the MIB1 labeling-index of the syndromic case with dysplasia (60.8% surface, 56.6% deep labeling indexes) was further enhanced in comparison with the other 2 syndromic cases. CONCLUSIONS: Sporadic and syndromic FGPs showed a neoexpression of Ck7, CEA, and mucin epitopes. As these markers are normal antigens of fetal stomach, FGPs showed a fetal, "immature" immunophenotype. The only difference we found between syndromic and sporadic polyps was a statistically significant enhanced MIB1-labelling index expression by syndromic FGPs, further enhanced in the syndromic FGP with dysplasia.

Adenomatous Polyposis Coli↗

Immunophenotyping of peroxidase-negative acute leukaemias using immunoalkaline phosphatase (APAAP) method.

Immunophenotyping of acute leukaemias has become an important diagnostic tool in haematology laboratories as it is now well recognised that the presence of certain surface markers has prognostic significance. In 1988, we experimented with the alkaline phosphatase anti-alkaline phosphatase (APAAP) method for immunophenotyping of leukaemic cells in our laboratory. 48 cases of peroxidase-negative acute leukaemias were studied. Our study showed that 2 peroxidase-negative cases carried myeloid surface markers, 44% were negative for the markers studied and 5% were unclassified due to technical problems. We concluded that the APAAP method is a useful technique for demonstrating cell markers in leukaemic cells as the reaction is reddish and usually intense. We failed to demonstrate surface markers in 44% of the cases probably because of the choice of a limited panel of monoclonal antibodies.

Adolescent↗

Ultrastructural demonstration of peroxidase expression in acute unclassified leukemias: correlation to immunophenotype and treatment outcome.

The lineage affinity of 57 cases of acute unclassified leukemias (AUL) was reevaluated by ultrastructural analysis of peroxidase expression (POEM) in combination with immunophenotyping and analysis of immunoglobulin gene configuration. Twenty-three cases of myeloid and three cases of megakaryocytic differentiation were identified by detection of ultrastructural myeloperoxidase (UMPO) and platelet peroxidase (UPPO). No significant correlation was noted between myeloid marker expression and POEM positivity, whereas presence of CD 19 or CD 24 antigen significantly correlated with POEM negativity (P = .001 and .023, respectively). Ig gene rearrangements including oligoclonal patterns were also recorded in 8 of 14 UMPO+ patients tested. Fourteen UMPO+ patients responded poorly to an ALL/AUL chemotherapy regimen with a low complete remission (CR) rate of 29% and a short median remission duration (MRD) of 5 months. The POEM- patients proved very heterogenous with respect to immunophenotype and Ig gene rearrangement. Seventeen of 21 patients tested had Ig gene rearrangements, including oligoclonal patterns. Combined data suggest that a proportion of these cases probably derive from a very immature lymphoid progenitor cell, particularly because 15 POEM- AUL patients showed a response to ALL/AUL chemotherapy comparable to that observed in patients with definitive acute lymphoblastic leukemia (ALL) (CR rate 80%, MRD 20 months). Thus, ultrastructural analysis of peroxidase expression can provide decisive prognostic information in AUL patients.

Acute Disease↗

Alveolar macrophages in idiopathic pulmonary fibrosis display a more monocyte-like immunophenotype and an increased release of free oxygen radicals.

Bronchoalveolar lavage (BAL) was performed in 13 patients with idiopathic pulmonary fibrosis (IPF) and in 10 control subjects. Free oxygen radical (FOR) production of alveolar macrophages (AM) and of blood monocytes was measured by luminol-dependent chemiluminescence (LDCL) without and after stimulation with zymosan A. We confirmed earlier studies that alveolar macrophages of IPF patients display a significantly elevated release of FOR under basic and under stimulated conditions. In contrast to alveolar macrophages, blood monocytes did not reveal altered LDCL in IPF. This indicates that the functional properties for augmented FOR release by IPF alveolar macrophages are acquired in the lungs and not in the peripheral circulation. To elucidate the possible mechanisms leading to the augmented LDCL response, immunophenotyping of alveolar macrophages was carried out. A panel of new monoclonal antibodies of the Ki-M-series, discriminating differentiation stages of monocyte/macrophage subpopulations, served for immunocytochemical staining. In IPF patients distribution of Ki-M2, Ki-M3, Ki-M6 and Ki-M8 positive AM demonstrated an increased proportion of alveolar macrophages expressing a more monocyte-like immunophenotype. Normally, monocytes as precursors of AM reveal a markedly stronger LDCL than alveolar macrophages themselves. Therefore, it seems likely that the increased LDCL of alveolar macrophages in IPF is due to the higher proportion of more immature monocyte-like cells in the alveoli of these patients.

Antibodies, Monoclonal↗

Peripheral T-cell lymphomas. Immunophenotype, lymphokine production, and immunologic functional characteristics of the lymph-node malignant T cells.

Immunophenotype and functions of the malignant T cells to secrete various T-cell derived lymphokines and to respond in autologous mixed lymphocyte reaction (AMLR) and allogeneic mixed lymphocyte reaction (MLR) of the six patients with peripheral T-cell lymphomas (PTL) are presented. Three cases showed CD3/TcR alpha beta discordance (1 CD3+/TcR alpha beta-; 2 CD3-/TcR alpha beta+) and one showed absence of both these antigens (CD3-/TcR alpha beta-). In addition, we found that 50% of cases expressed CD25+, CD38+, and CD71+ activation antigens. The CD3/TcR alpha beta discordance and expressions of activation antigen noted in these cases were typical and similar to those reported from elsewhere. These malignant T cells from all cases whether CD25+ or CD25- (resting) expressed elevated interleukin-2 receptors (IL-2R) on stimulation with phytohemagglutinin (PHA) or human recombinant interleukin-2(rIL-2), and secreted elevated IL-2 by PHA, than do T cells from patients with tuberculosis (TB) or normal healthy controls. These malignant T cells also demonstrated elevated AMLR but deficient MLR B cells growth factor (BCGF) (except in one unusual case) secretion was increased, whereas B-cell differentiation factor (BCDF) secretion decreased. These results suggest that malignant T cells from lymph nodes of patients with PTL have uniform multiple immunologic defects in IL-2, BCGF, and BCDF lymphokine secretion and respond in AMLR and MLR, which do not correlate with immunophenotype or histologic types. These functions differentiate them from lymph-node T cells of patients with TB or blood T cells of normal healthy controls.

Aged↗