Lymphocyte Surface Antigens Research Articles

The HIV-1 Nef protein shares an antigenic determinant with a T-cell surface protein

To characterize antigens on uninfected T lymphocytes reactive with monoclonal antibodies (MAb) directed against the HIV-1 Nef protein, and to search for antibodies directed against this epitope in HIV-1-infected individuals. Murine MAb directed against an epitope of Nef defined by amino acids 60-73 reacted with cell surface antigens of normal peripheral blood lymphocytes and permanent human T-cell lines. The specificity of the MAb reaction was investigated by flow cytometry and immunofluorescence. The antigen was precipitated from lysates or uninfected cells using MAb or sera from HIV-1-infected individuals and analysed by Western blot and isoelectrofocusing. An antigen with an apparent relative molecular mass of 137,000 and an isoelectric point of 8.45 was immunoprecipitated with the cross-reactive MAb from uninfected human T cells. Sera from HIV-positive individuals recognizing a Nef epitope partially overlapping with the binding site of the cross-reactive MAb stained the 137 kD protein precipitated with the MAb in Western blot analysis, while HIV-positive sera without antibodies to this Nef region and sera from uninfected individuals were negative. The induction of autoantibodies cross-reactive with cellular surface proteins may play a role in the pathogenesis of AIDS.

Distribution and function of lymphocyte surface antigens. Molecules costimulating T lymphocyte activation and effector function.

Annals of the New York Academy of SciencesVolume 677, Issue 1 p. 86-93 Distribution and Function of Lymphocyte Surface Antigens Molecules Costimulating T Lymphocyte Activation and Effector Function LEWIS L. LANIER, LEWIS L. LANIER DNAX Research Institute of Molecular and Cellular Biology Palo Alto, California 94304Search for more papers by this author LEWIS L. LANIER, LEWIS L. LANIER DNAX Research Institute of Molecular and Cellular Biology Palo Alto, California 94304Search for more papers by this author First published: March 1993 https://doi.org/10.1111/j.1749-6632.1993.tb38768.xCitations: 9AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume677, Issue1Clinical Flow CytometryMarch 1993Pages 86-93 RelatedInformation

Lymphokine production by mesenteric lymph node cells from BALB/c mice during Hymenolepis nana infection

Mesenteric lymph node cells (MLNC) prepared from BALB/c mice during infection with Hymenolepis nana proliferated extensively when cultured in the presence of soluble egg antigen, as assessed by measuring 2H-thymidine incorporation. Analysis of Hymenolepis-specific proliferative cells in MLNC by using monoclonal antibody specific for mouse T lymphocyte surface antigens revealed that the proliferative response of MLNC was mediated by Thy-1,2 +, L3T4 − cells, that is, helper T cells. Supernatant of MLNC cultured with egg antigen contained large amounts of interleukin-2 and interferon-γ, but only low levels of interleukin-5. The titer of these cytokines did not correlate with the interval between oral infection and collection of MLNC. These results strongly indicate that the Th1 subtype of helper T lymphocytes respond well to stimulation of H. nana egg antigen and suggest that acute inflammatory responses are involved in host-protective immunity to H. nana.

Lymphocyte subsets recirculate from blood to lymph at different rates in conscious sheep

Lymphocytes migrate and recirculate continuously between blood and lymph. The current study compared the migratory properties of lymphocyte subsets by labelling lymphocyte surface antigens and analysing simultaneous samples of mesenteric lymph, systemic arterial blood and mesenteric venous blood from conscious sheep. The lymphocyte output in lymph averaged 5.33 +/- 0.89 x 10(6) min-1 (lymph flow rate of 92 +/- 13 microliters min-1, lymphocyte count 61.9 +/- 10.7 x 10(9) l-1, n = 10) and the proportion of cells which carried the CD4 antigen (CD4+) was considerably higher in lymph (46 +/- 3%) than in arterial blood (23 +/- 2%; p < 0.01, n = 9). This increase was paralleled by a small but statistically significant decrease in the percentage of CD4+ cells in mesenteric venous blood (20 +/- 2%), as compared with systemic arterial blood (26 +/- 2%; p < 0.05, n = 6), which is consistent with the hypothesis that CD4+ cells migrate out of the blood vessels, and recirculate through the lymphatics, more readily than other lymphocyte subsets.

Homing of CD8CD57 T lymphocytes into acutely rejected renal allografts.

This study compares the cellular events in excised rejected renal allografts (RKT), with concurrent data in the peripheral blood (PB) in the same patients. The kidney transplants were obtained from recipients after rejections crises that were refractory to treatment. Two-color flow cytometry data was used for quantitation of cell subset profiles and quantitation of the density of individual lymphocyte surface antigen(s). The level of CD3DR-positive T cells in RKT was significantly higher than in PB. This difference ranged from 3 to 19-fold increases. There was an even more pronounced increase in CD8CD57 cell subset levels in RKT versus PB. In parallel with these findings, there was a 15-fold greater mean density of the CD8CD57 markers on T cells in RKT, when compared with the same cells in PB. The density of CD8 and of DR markers on CD3+ cells was also significantly higher (4-fold in each instance) in RKT. These data point to a homing of CD8CD57 cells with corresponding increases in the density of these markers in acutely rejected renal allografts, with only a relative decrease of this cell subset in peripheral blood. The appearance of a high preponderance of CD8CD57 cells in the renal allograft at the time of a rejection crisis may constitute a particularly severe prognostic sign regarding the reversibility of the response after treatment with steroids and/or monoclonal antibodies.

Reactivity of some monoclonal antibodies specific for human lymphocytes with vervet monkey peripheral blood mononuclear cells.

Reactivities of some monoclonal antibodies to human lymphocyte surface antigens were tested on vervet monkey peripheral blood mononuclear cells (PBMC), using flow cytometry and immunoperoxidase techniques. A number of antibodies were identified which reacted with similar populations of lymphocytes from vervet monkeys. These included antibodies that define T cells, suppressor/cytotoxic cell subset, pan B cells, monocytes and MHC class I and II. A number of anti-CD4 markers examined were unsuitable for use in the vervet system.

Thy-1, the enigmatic extrovert on the neuronal surface.

Thy-1 is a small glycoprotein of 110 amino acids which, folded in the characteristic structure of an immunoglobulin variable domain, are enchored to the plasma membrane via a glycophosphatidylinositol (GPI) tail (Fig. 1). It is a major component of the surface of various cell types, including neurons, at certain stages of their development. These qualities doubtlessly appeal to certain cognoscenti, but it is not clear why they would raise Thy-1 to the status of a favourite molecule. Indeed, few scientists readily admit to having a favourite. We study individual molecules because science is rooted in specific observations; but we do so in order to discover mechanisms of general importance. A molecule's appeal is dependent on its ability to reveal novel aspects of how nature works. Thy-1 has been unusual in this respect. It was the first lymphocyte surface antigen shown to be restricted to a functional subset of lymphocytes (T cells in the mouse), a finding crucial to the development of cellular immunology; it was one of the first cell surface molecules to be sequenced and indicated the importance of immunoglobulin domains and GPI anchors as structural motifs; it has been pivotal in studies demonstrating that GPI-anchored molecules are able to signal across the membrane they do not span. Thy-1 has revealed this much, however, with the charm of an adroit stripper: it has always promised glimpses of things more exciting than that displayed. In particular, the function of this molecule has never emerged.(ABSTRACT TRUNCATED AT 250 WORDS)

A phenotypic and genotypic study of three node-based, low-grade peripheral T-cell lymphomas: angioimmunoblastic lymphoma, T-zone lymphoma, and lymphoepithelioid lymphoma.

Phenotypic and genotypic findings were correlated and compared for 35 specimens taken from 34 patients with three specific types of low-grade peripheral T-cell lymphoma: lymphoepithelioid (LeL), angioimmunoblastic (AILD), and T-zone (TzL) lymphoma. Frozen sections were stained by the double immunoenzymatic method using a combination of the monoclonal antibody Ki-67 for proliferating nuclei and those against lymphocyte surface antigens. Data were correlated by observing clonal rearrangements in the genes of the T-cell receptor beta chain (TCR beta). Of the 35 specimens studied, 32 (91%) were of predominantly CD4+ helper cell proliferation, and 21 (60%) showed the TCR beta gene rearrangement. There were 15 cases of AILD and TzL with predominantly helper cell proliferation, which contained a minimum of 21% CD4+Ki-67+ cells based on the total number of cells present in the specimen. Of these, 13 (87%) showed TCR beta rearrangement. In eight cases, containing a maximum of 20% CD4+Ki-67+ cells, only one (13%) showed any rearrangement. In addition, TCR beta rearrangement was observed in five of the nine cases of LeL, including two cases with only 12% CD4+Ki-67+ cells. For each of the three types, the proportion of CD4+ cells among the Ki-67+ population showed a relatively good correlation with the clonal TCR beta gene rearrangement. Moreover, there was a significant difference (P less than 0.05) in survival curves between groups with and without TCR beta rearrangement, although no obvious plateau was seen. These results suggest that the paucity of tumor cells in these lesions may account for the absence of a detectable band of rearrangements in some patients with one of these three specific types of low-grade peripheral T-cell lymphoma.

Surgical influence on murine immunity and tumor growth: relationship of body temperature and hormones with splenocytes.

Adrenalectomy predisposed the C3HeB/FeJ Mouse to tumor from a low dose of tumor cells, derived from a C3H spontaneous mammary adenocarcinoma. Sham surgery had a similar effect. In contrast, ovariectomized females, intact females, and male mice did not allow the low dose of cells to develop into a tumor. In order to better understand the role of hormones on the immune system controlling tumor growth, normal C3HeB/FeJ mice were studied for the effect of corticosterone or estradiol on splenic lymphocyte surface antigen expression. Adrenalectomy and ovariectomy caused a decrease in the percentage of all T cell subclasses and an increase in absolute numbers of immunoglobulin-bearing cells. Reconstitution of ovariectomized mice with estradiol did not significantly alter lymphocyte cell surface antigen expression. In contrast, injection of corticosterone into adrenalectomized mice brought these values to normal. Further study on normal mice placed on a 12:12-hr light:dark schedule showed that the hours after lights on (HALO) had a significant effect (analysis of variance) on body temperature, percentage of splenic B cells, T pan, T helper and T suppressor cells, and absolute numbers of T pan cells. Brain dehydroepiandrosterone sulfate correlated positively with T pan lymphocytes, but showed no significant effect on HALO. In contrast, body temperature showed a strong circadian rhythm (P less than 0.001). In addition, the presentation of estrus was circadian rhythmic (P = 0.003) with 58% of mice in estrus at 16 HALO and only 8% at 4 HALO. Multiple regression analysis revealed body temperature was strongly associated with absolute numbers of splenic T lymphocytes and their subsets, as well as percentage of B lymphocytes, Thy 1.2-, and Lyt-2-bearing cells. Similarly, HALO and estrous cycle stage were associated with percentage of T helper cells. The data showed that body temperature and hormones were associated with the cell surface antigens on lymphocytes and suggest that they affect lymphocyte function.

Phenotypic and genotypic identification of human lymphocytes and their application for diseases.

Lymphocytes are called “nature's best known cells”, since their function has been studied in detail by many aggressive immunologists and their surface phenotypes have been investigated thoroughly with the monoclonal antibodies (MAbs) to surface antigens of lymphocytes. In addition, a surprisingly rapid progress of gene engineering, including that of immunoglobulin and T cell receptor has been used for the investigation of lymphocyte genotypes. This knowledge was directly applied for the analysis and diagnosis of lymphoid diseases.

Detection of Human T-Cell Lymphotropic Virus Type I-related Antibodies in Patients with Lymphocytic Interstitial Pneumonia

Lymphocytic interstitial pneumonia (LIP) is a rare form of interstitial pneumonia with infiltration of mononuclear cells in the interstitium, the pathogenesis of which is unknown. We studied six patients with LIP to investigate the immunologic characteristics of lymphocytes in the lower respiratory tract and the possible involvement of human T-cell lymphotropic virus type I (HTLV-I), which is endemic in the southwestern region of Japan. Lymphocyte surface antigen phenotyping in peripheral blood (PB) and bronchoalveolar lavage fluid (BALF) cells revealed a predominance of CD8 positive (suppressor/cytotoxic) T-lymphocytes (PB: 51.5 +/- 0.8%; BALF: 52.9 +/- 12.7%), which consisted of an increased number of CD8 positive CD11 negative (cytotoxic) T-lymphocytes (PB: 30.2 +/- 10.5%; BALF: 57.1 +/- 11.8%). The increased number of cytotoxic T-lymphocytes among patients with LIP led us to investigate the possible involvement of HTLV-I, EB virus, and HIV in patients with chronic interstitial disorders of LIP, sarcoidosis, and IPF. The seropositivity rate for HTLV-I was 83.7% (5/6) in patients with LIP, 3.1% (1/28) with IPF, 7.1% (2/28) with sarcoidosis, and 0% (0/28) in healthy volunteers. None of the patients were seropositive for either HIV or EB virus. These results suggest that HTLV-I may be involved in a direct or indirect role in the pathologic mechanisms through the host immune reaction to the antigenicity of the virus and/or the possible involvement of viral regulatory genes to disrupt the normal immune reaction of the host.

Papular Acrodermatitis of Childhood (Gianotti‐Crosti Disease)

An 11-year-old boy had lentil-sized lichenoid papules, localized to the limbs and trunk, together with acute, nonicteric, hepatitis B surface antigen-positive hepatitis. The clinical picture and course were typical of Gianotti-Crosti disease. Monoclonal antibodies were used to study the lymphocyte subpopulations and surface antigens in the inflammatory infiltrate in frozen sections of a skin biopsy specimen. The results provide data on the pathogenic mechanism of the papular exanthem.

Protein-tyrosine-phosphatase CD45 is phosphorylated transiently on tyrosine upon activation of Jurkat T cells.

The leukocyte common antigen (CD45) is an abundant lymphocyte surface antigen that has been reported to be involved in signaling through the T-cell antigen receptor. CD45 is a transmembrane protein-tyrosine-phosphatase. An internal segment comprises two domains each of which is homologous to other protein-tyrosine-phosphatases; the extracellular segment has the hallmarks of a ligand-binding motif. Since tyrosine phosphorylation is an early signal resulting from stimulation of the T-cell antigen receptor and CD45 is required for proper activation through the receptor, we explored whether CD45 might be regulated by tyrosine phosphorylation. Treatment of a T-cell leukemia line (Jurkat) with either phytohemagglutinin or anti-CD3 antibodies induced phosphorylation of tyrosine residues in CD45; treatment with phorbol 12-myristate 13-acetate did not. Phosphorylation of CD45 was transient, disappearing within 40 min after phytohemagglutinin treatment. The requirement for stringent conditions of phosphatase inhibition suggests that CD45 is capable of autodephosphorylation in vivo. These observations support recent reports indicating CD45 is involved in an early step in the T-cell activation cascade. They also suggest that phosphorylation/dephosphorylation of tyrosine residues in CD45 should be explored further as a possible regulatory mechanism.

Effect of ubenimex on the immune system of patients with hematological malignancies

The effect of in vivo administration of ubenimex (Bestatin) on the immune status of patients with hematological malignancies in remission was studied. Natural killer (NK) cell activities, lymphokine activated killer (LAK) cell activities, production of interferon-γ (γ-IFN) and surface antigens of peripheral lymphocytes were examined before and after administration of ubenimex. Analysis of the T, B and NK cell compartment ax conducted by assessing expression of the following antigens: CD3 + CD19 −(T), CD3 −CD19 +(B), CD8 +CD11b −(Tc), CD8 +CD11b +(Ts), CD4 +Leu8 −(Th), CD4 +Leu8 +(Ti), CD16CD57 (NK) using a 2-color flow cytometric analysis. NK and LAK activity was significantly lower in patients with hematological malignancies as compared to normal subjects. The absolute numbers of lymphocytes and NK cells were also lower than those in healthy controls. The reduced NK and LAK activity, however, was elevated after ubenimex administration. The absolute numbers of helper T cells, cytotoxic T cells and NK cells were also increased after administration of the drug. These findings were not observed in patients treated without ubenimex. Serum levels of IFN-γ were not markedly changed after ubenimex administration. But peripheral blood mononuclear cells cultured with rIL2 showed appreciable levels of IFN-γ production, and production increased after ubenimex administration. These results shows that ubenimex is a powerful immunomodulator that augments or restores some immune functions in patients with hematological malignancies. ubenimex/NK activity/LAK activity

Preparation and characterization of a monoclonal antibody against bovine CD5 lymphocyte surface antigen

The M1 monoclonal antibody (mAb) was proved to recognize 51–70% of Bovine peripheral blood lymphocytes (PBL). The M1+ cells were SIg-. In spleen and lymph nodes, the M1 positive lymphocytes were located within the T cell areas. All the lymphoid follicles remained negative. In the thymus, 10% of thymocytes were M1+, most of them were located in the medulla. The M1 mAb did not inhibit spontaneous rosette formation by sheep erythrocytes and bovine lymphocytes. On the other hand, biochemical analysis of membrane antigen with bovine thymic tumor cell line LB203 gave a molecular weight of 75 kDa. Despite a slight difference in biochemical results (75 vs 67–69 kDa). Our data permit us to consider M1 mAb as a possible homologous of human anti-CD5 mAb. Finally, M1 cross-reacted with sheep peripheral blood T lymphocytes.

Epitopes of the T19 lymphocyte surface antigen are extensively conserved in ruminants

The reactivity of five monoclonal antibodies (mAbs SBU-T19, 197, IL-A29, CC-15 and CC-39) specific for the T19 molecule on sheep and cattle CD4-CD8-T cells was compared. MAbs SBU-T19 and 197 were shown to recognise separate epitopes on T19. All mAbs reacted with lymphocytes from several different ruminant species and the tissue distribution and frequency of positive cells was similar in each case. None of the mAbs reacted with horse, pig or camel lymphocytes. The extensive conservation of T19 epitopes in ruminants during the mammalian radiation could indicate an important role for this molecule in the ruminant immune system.

T lymphocyte surface antigen markers in osteoporosis

Two distinct syndromes of osteoporosis have been postulated: type I, which is characterized by accelerated bone loss occurring in women during the early postmenopausal period; and type II, an age-related process of bone loss affecting both men and women in and after the seventh decade. Recently there has been indirect evidence linking local products of the immune system with bone remodeling. We therefore studied peripheral blood profiles of specific lymphocyte phenotypes in women with type I osteoporosis and in older women and men with type II osteoporosis. The ratio of CD4-bearing (T helper) cells to CD8-bearing (T cytotoxic-suppressor) cells (CD4/CD8 ratio) was elevated in women with symptomatic type I disease. In addition there was a significant negative correlation (r = -0.62, P less than 0.001) between the CD4/CD8 ratio and the spinal bone mineral density measured by dual-photon absorptiometry. In contrast, older men with a history of fracture (hip or spine) had CD4/CD8 ratios similar to control men. The number of T cells bearing IL-2R or VLA-1 was not different between osteoporotic subjects and controls in either men or women. This study supports the concept that local products of the immune system may be directly or indirectly involved in the pathogenesis of type I osteoporosis.

Differential effects of eight metal ions on lymphocyte differentiation antigens in vitro

In vitro studies were conducted to determine the effects of metal ions known to be released from metallic implants in vivo on the expression of lymphocyte surface antigens. Normal human peripheral blood lymphocytes were exposed to various concentrations of metal ions (Fe3+, Ni2+, Co2+, Mo6+, V5+, Cr6+, Cr3+, and Ti3+) for 30 min at 37 degrees C in a 5% CO2 atmosphere, and then analyzed for their ability to form rosettes with sheep red blood cells. Following this preliminary analysis, lymphocytes were exposed to the metal ions found to inhibit the E-rosette reaction (Fe3+, Ni2+, and Co2+) in order to determine which of the following surface antigens were affected: CD2, CD3, CD4, CD8, CD1, CD22, CD10, and HLA-DR. Our results showed that the in vitro treatment of lymphocytes with Fe3+ or Co2+ caused inhibition of CD2 only, whereas Ni2+ caused inhibition of both CD2 and CD3 antigens. These findings suggest that Fe3+, Co2+, and Ni2+ ions may interfere with T cell activation since both CD2 and CD3 are involved in that process.

Assessment of local cellular immunity in lung cancer by bronchoalveolar lavage

Small cell lung cancer (SCLC) is the most malignant of the pulmonary neoplasms and is associated with a poor local cellular immune response. 16 patients with non small cell lung cancer (NSCLC) and 11 patients with SCLC underwent bronchoalveolar lavage (BAL) in the lung which harbored the tumor in order to investigate the lymphocyte surface antigens utilizing the immunoperoxidase technique. Analysis of blood lymphocytes was performed in parallel. 8 patients with previous sarcoidosis in complete remission who underwent BAL and 10 normal blood donors served as controls. Among blood lymphocytes the CD3+, CD4+ and CD16+ cell populations were elevated significantly and the T4/T8 ratio was elevated in NSCLC patients, but only CD16+ were augmented in SCLC. Cell populations expressing the activation markers transferrin (TF) receptor, interleukin-2 (IL-2) receptor and the very late antigen VAL-1 were also increased in NSCLC, while SCLC was associated with antigen distributions similar to controls. No differences between the cohorts were seen in the expression of human leukocyte antigen (HLA)-DR. In BAL the population of CD3+ and CD4+ cells were reduced in SCLC and the T4/T8 ratio was diminished in contrast to controls and NSCLC patients, whereas these two latter groups did not differ from each other. The distribution pattern of CD16, TF receptor and IL-2 receptor in the study groups resembled that of cells of the blood stream, but CD16+ natural killer cells were additionally down regulated to control values in SCLC. No differences were seen in the distribution of VLA-1. HLA-DR+ cells were clearly elevated in both cancer groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Treatment with Biosynthetic Human Growth Hormone (GH) on Peripheral Blood Lymphocyte Populations and Function in Growth Hormone-Deficient Children

GH influences the immune response. The mechanism is not known; however, the presence of receptors for GH on human lymphocytes as well as its ability to influence and modulate immune responses in animals suggest an association between GH and immune function in man. We evaluated the effect of recombinantly derived natural sequence human GH (hGH) on lymphocyte surface antigen expression, response to mitogenic stimulation, expression of interleukin-1 receptors, and production of anti-hGH antibodies in GH-deficient children. The only observed changes were a decrease in the percentage of B-cells and a transient increased reactivity to phytohemagglutinin stimulation. It appears from the results of our studies that the administration of hGH has a selective effect on lymphocyte immune function; however, we cannot eliminate a role for hGH in the initiation or regulation of antigen-mediated immune responses.