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PubMed1984

The T4 surface antigen is involved in the induction of helper function.

The OKT4 monoclonal antibody reacts with a 62K m.w. glycoprotein present on a subset of human T cells with the capacity to help or induce B cell differentiation. The present studies were undertaken to determine whether the T4 molecule itself plays any role in the helper function mediated by T4+ cells. Using a series of monoclonal antibodies (OKT4, OKT4A-E), which react with distinct noncompeting epitopes of the T4 molecule, we found that OKT4A and OKT4E, but not OKT4, antibodies inhibited the induction of B cell differentiation by T4+ cells. This inhibition was apparent when using nonirradiated or irradiated T4+ cells, and was noted over a wide range of concentrations. Importantly, inhibition occurred only if the antibody was present during the first 24 hr of cell culture, and the presence of antibody did not alter the kinetics of induction of B cell differentiation. Thus, these data suggest that the T4 molecule plays an early, critical role in cellular interactions required for helper cell function.

Antibodies, Monoclonal↗
PubMed1984

Biologic functions of the OKT1 T cell surface antigen. I. The T1 molecule is involved in helper function.

The OKT1 (Leu-1) monoclonal antibody reacts with a 69 KD glycoprotein that is present on only a fraction of functionally mature thymocytes but is maintained on most peripheral T cells. In the study presented, we examined the role of this surface molecule in T cell function. We found that addition of the OKT1 antibody to B cells and autologous T4+ cells markedly enhances B cell differentiation. This enhancement was apparent when nonirradiated or irradiated T4+ cells but not T8+ cells were used. Moreover, the OKT1 antibody as well as the OKT1 F(ab')2 fragment enhanced B cell differentiation in a dose-dependent fashion. It is important to note that perturbation of the T1 molecule with OKT1 in the presence of autologous E- cells causes the rapid release of molecules that trigger B cells to proliferate and differentiate into Ig-secreting cells. These data when considered together suggest that OKT1 reacts with a T cell membrane determinant or a complex that is intimately involved in the execution of helper function on OKT4+ cells.

Antibodies, Monoclonal↗
PubMed1983

Biological functions of T-cell surface glycoproteins.

The OKT4 monoclonal antibody reacts with a 62 KD cell surface glycoprotein present on a subset of human T cells with the capacity to help or induce B-cell differentiation. The OKT8 monoclonal antibody reacts with a 76 KD cell surface glycoprotein present on a subset of human T cells with the capacity to suppress B-cell differentiation. The current studies were undertaken to determine whether the T4 and/or T8 antigens themselves play any role in the helper or suppressor function mediated by OKT4+ or OKT8+ cells. Specifically, we asked if monoclonal antibodies that react with noncompeting epitopes on the T4 or T8 molecules could block helper or suppressor function. Isolated human B cells were triggered in vitro to differentiate into antibody-forming cells (AFC) by autologous OKT4+ cells and macrophages in the presence or absence of OKT4 antibodies. By means of a reverse hemolytic plaque assay, AFC were detected as plaque-forming cells (PFC). We found that OKT4A, but not OKT4, antibody inhibited the PFC response over a wide range of concentrations. The antibodies OKT4B, OKT4C, OKT4D, OKT4E inhibited the PFC response to varying degrees. Importantly, inhibition by OKT4A occurred only if the antibody was present during the first 24 hours of cell culture. In the second set of experiments, OKT8+ cells were added to cultures containing B cells, and OKT4+ cells in the presence or absence of OKT8 antibodies, PFC activity was measured 7 days later. We found that the addition of OKT8E or OKT8G, but not OKT8B, OKT8C, OKT8D, OKT8F, or OKT8H, antibodies significantly inhibits the suppressor function mediated by OKT8+ cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1983

[Granulocytic progenitors in bone marrow autografts].

Granulocytic progenitor cells (CFC) are a better reflection of stem cell pools than precursors. Their total number can be estimated during hematologic steady-state (N = 70 +/- 29 x 10(5) CFC/kg); the amount of marrow necessary to perform a bone marrow transplantation is only 1% of the total pool. CFC are useful but have a mainly qualitative value in evaluating the viability of marrow stored for 24 h at room temperature (92%) or marrow thawed after DMSO cryopreservation (62%). Sequential study of CFC in patients receiving autologous marrow transplantation enables differentiation of engraftment from autologous recovery. In 11 recipients of autologous marrow transplantation, no statistical relation was observed between number of infused CFC and severity of granulocytopenia. Further studies will be necessary to evaluate a better marker of real hematopoietic stem cells.

Adolescent↗
PubMed1983

Pathologic processing of vitrectomy specimens. A comparison of pathologic findings with celloidin bag and cytocentrifugation preparation of 102 vitrectomy specimens.

Specimens obtained from 102 vitrectomies were processed by cytocentrifugation and celloidin bag techniques. The histopathology obtained with each procedure was compared with respect to cellular and tissue findings. Forty-five percent of cases had identical findings by the two techniques. Quantitative analysis of the discrepancies revealed better cellular recovery and identification by cytocentrifugation, and similar rates for the recovery and identification of tissue elements. Qualitative analysis showed better demonstration of tissue histopathology using celloidin bag thin sections. Thus, pathologic analysis was more complete when the two techniques were used together than when either was used alone.

Centrifugation↗
PubMed1980

MLC-derived human helper factor(s) that promote B cell differentiation: induction, functional characterization, and role of Ia antigens.

Utilizing a PFC assay to quantitate the polyclonal activation of human peripheral blood B lymphocytes, we have investigated the induction and functional activity of MLC-derived human helper factor(s). Our data demonstrate that highly purified responder T cells, but not B or null cells, are required for the elaboration of MLC helper factor(s) that trigger the in vitro differentiation of B lymphocytes into PFC. Helper factor can trigger B cell maturation in the absence of helper T cells, since complement- (C) mediated lysis of the small (less than 5%) fraction of T cells present in anti-F(ab)2 immunoabsorbent column purified B cell population eliminates the PWM induced, but not the helper factor-induced PFC response. Responder T cells required for helper factor production do not bear surface membrane Ia, since alpha p23,30 + C treatment of this population does not affect helper factor generation. In contrast, alpha p23,30 + C treatment of the allogeneic stimulator cell population eliminates helper factor production. Taken together, these results demonstrate that interaction between Ia-bearing stimulator cells and Ia- responder T cells is required for the production of MLC-derived helper factor. In additional experiments, we determined that alpha p23,30, in the absence of C, totally abrogates the PFC response triggered by MLC helper factors. This result suggests an important role for Ia antigens in the functional activity of preformed helper factor molecules.

Antibodies↗
PubMed1981

Functional analysis of human T cell subsets defined by monoclonal antibodies. III. Regulation of helper factor production by T cell subsets.

In the present report we extended our previous studies demonstrating that obligatory T-T interactions are important in regulating human immune responses in vitro. Functionally distinct human T cell subsets were isolated by complement-mediated lysis using the monoclonal antibodies OKT4 and OKT8. Evidence was obtained that during allogeneic interactions, OKT4+, but not OKT8+, responder T cells are required to generate helper factor(s) capable of polyclonally activating human B cells independent of additional T cell help. Importantly, the alloantigen-induced helper factor(s) production and/or release was found to be suppressed by addition of graded numbers of radiosensitive OKT8+ cells. On the other hand, no evidence was obtained that supernatant derived from alloactivated OKT8+ cells could counterbalance the helper activity generated in the presence of supernatant from alloactivated OKT4+ cells. Furthermore, OKT8+ cells, known to suppress PWM-driven B cell differentiation in the presence of OKT4+ cells, do not suppress B cell differentiation induced by preformed helper factor even in the presence of OKT4+ cells. These data further underscore the importance of functional T-T interactions in immunoregulation in vitro and support the idea that the target of suppression of B cell differentiation, induced either by alloantigen-triggered helper factor or PWM, are OKT4+ cells and not B cells themselves.

Antibodies↗
PubMed1982

Characterization of the alloactivated E+Ia+ cell capable of stimulating in mixed lymphocyte culture.

Human peripheral blood E+ lymphocytes were alloactivated by E- cells and then purified by repeat E+ selection. As described by others, alloactivated cells (E+d6) but not unactivated E+ cells were capable of stimulating both allogeneic and autologous mixed lymphocyte cultures (MLC). To further characterize the subset of cells responsible for this function, we used a variety of monoclonal antibodies to human T cells and monocytes. Treatment of E+d6 cells with anti-Ia OKI1) plus complement (C) abrogated their stimulating capacity. In contrast, treatment with the anti-T cell antibodies OKT3, OKT11A, OKT4, OKT8 plus C or anti-macrophage antibody (OKM1) plus C failed to eliminate their MLC stimulatory capacintibodies to human T cells and monocytes. Treatment of E+d6 cells with anti-Ia OKI1) plus complement (C) abrogated their stimulating capacity. In contrast, treatment with the anti-T cell antibodies OKT3, OKT11A, OKT4, OKT8 plus C or anti-macrophage antibody (OKM1) plus C failed to eliminate their MLC stimulatory capacintibodies to human T cells and monocytes. Treatment of E+d6 cells with anti-Ia OKI1) plus complement (C) abrogated their stimulating capacity. In contrast, treatment with the anti-T cell antibodies OKT3, OKT11A, OKT4, OKT8 plus C or anti-macrophage antibody (OKM1) plus C failed to eliminate their MLC stimulatory capacity. Because OKT3 recognizes the majority of T cells and OKT11A recognizes virtually all E+ cells, we reasoned that a contaminating non-T cell containing the MLC-stimulating capacity may be present within the alloactivated E+ population. To further address this question, E+d6 cells were positively and negatively selected using a rosetting technique with anti-Ig-coated red cells. The positively selected OKT3, OKT11A, OKT4, or OKT8 E+d6 cells retained minimal ability to stimulate MLC, whereas the corresponding negatively selected populations were highly enriched in this function. Phenotypic analysis of the isolated populations failed to demonstrate greater than 1% surface membrane Ig(SmIg) positive cells. Taken together, these results suggest that the MLC stimulatory capacity of alloactivated E+ cells is contained within an Ia+, OKM1-, SmIg- non-T cell subset.

Antibodies, Monoclonal↗
PubMed1982

Functional analysis of human T cell subsets defined by monoclonal antibodies. V. Suppressor cells within the activated OKT4+ population belong to a distinct subset.

In the present report, we characterize a monoclonal antibody directed at a surface differentiation antigen on human T cells. The monoclonal antibody, OKT17, recognizes a cell surface antigen present on the majority of resting normal peripheral T cells. In contrast, OKT17 is unreactive with normal B cells, B cell lines, T cell lines, or SIg+ CLL. Interestingly, after activation, the antigen recognized by OKT17 is lost from a subset of OKT4+ cells. We took advantage of this finding to explore further the functional heterogeneity within activated OKT4+ cells. Evidence was obtained that the PWM-activated OKT4+ subset remaining after depletion of OKT17-reactive T cells (OKT4+ 17-) contains radiosensitive helperr cells but is devoid of suppressor cells. In contrast, the activated OKT4+ 17+ population contains potent radiosensitive suppressor cells as well as radioresistant helpe cells. Taken together, these studies suggest that the OKT17 monoclonal antibody can differentiate two functionally mature, activated OKT4+ human T cells: OKT4+ OKT17+ radiosensitive suppressor cells and OKT4+ 17- radiosensitive helper cells.

Antibodies, Monoclonal↗
PubMed1984

Fractionation of skin tumor-initiating activity in coal liquids.

Narrow temperature range distillates from biologically active solvent refined coal-I and -II heavy-end coal liquids were fractionated according to chemical class and assayed for initiation of skin carcinogenesis in CD-1 mice. In addition, instrumental chemical analyses were performed on the distillates and their chemical fractions. Results showed that initiation activity in these complex fuel mixtures could be segregated both by boiling point and chemical class. Neutral polycyclic aromatic hydrocarbon fractions were the most active of the chemical classes, with some initiating activity being shown by nitrogen-containing polycyclic aromatic hydrocarbon. Aliphatic and hydroxylated polycyclic aromatic hydrocarbon fractions showed little or no initiating activity. For the two solvent refined coal-II distillates studied, initiating activity was substantially higher in the material boiling above 850 degrees F than in that boiling 800-850 degrees F, although both contained essentially the same concentrations of benzo[a]pyrene. These data indicate that the overall initiating activity of these complex mixtures is highly dependent on interactions of the many chemical carcinogens and that relative concentrations of known carcinogenic polycyclic aromatic hydrocarbons, such as benzo[a]pyrene and dimethylbenz[a]anthracene, are not the sole determinants of initiating activity.

Animals↗
PubMed1984

ECG abnormalities in polymyositis.

Electrocardiographic abnormalities were found in 25 (32.5%) of 77 patients with polymyositis. Left anterior hemiblock (13.0%) and right bundle-branch block (9.1%) were the most common abnormalities. No association could be found between these defects and clinical activity of polymyositis, severity of duration of disease, or degree of creatine kinase level elevation. Similarly, there was no association with age or the presence of certain clinical conditions such as rash or arthritis. In only two patients, both children, did an ECG abnormality improve with corticosteroid therapy. Three patients with heart block died suddenly. This study points up the need for continual close observation of patients with inflammatory muscle disease, even after apparent remission.

Adolescent↗
PubMed1984

Serum immunoglobulin elevations in the acquired immunodeficiency syndrome (AIDS): IgG, IgA, IgM, and IgD.

The exact nature of the immune defect in the acquired immune deficiency syndrome (AIDS) is not known. Most studies have focused on abnormal T-cell functions which occur in AIDS. Although polyclonal elevation of serum immunoglobulins is also consistently reported in AIDS, there have been no statistical studies measuring the isotypes (classes) comprising this hypergammaglobulinemia. Quantitative serum immunoglobulin levels of IgG, IgA, IgM, and IgD in patients with AIDS (n = 33) were compared to healthy homosexual (n = 71) and healthy heterosexual (n = 32) controls. Serum IgD levels are increased tenfold in AIDS compared to healthy heterosexuals, and threefold compared to healthy homosexuals. Serum IgA levels are increased more than twofold that of either control group. In contrast, the elevations of IgG and IgM are relatively small and show much greater overlap compared to controls. We conclude from a statistical analysis of the data that these elevations of IgD and IgA are characteristics of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

[Triggering of human peripheral blood B cells by supernatants of activated T cells: the role of Ia-like determinants].

Human peripheral blood B lymphocytes, isolated by Sephadex G-200 anti-Fab column chromatography, were non specifically induced by either pokeweed mitogen (PWM) or soluble products of antigen stimulated T cells, to differenciate into plaque directed against human Ia-like antigens (anti-p 23-30) inhibited the differenciation of B cells into antibody forming cells. Thus, while PWM induced proliferation was only mildly reduced by anti-p 23-30, the PWM induced PFC response was totally abrogated. Conversely, the antiserum abolished both the proliferative and the PFC responses generated by products of activated T cells. Using both Ouchterlony plates and co-precipitation techniques, we were unable to detect p 23-30 molecules on the active products present in the T cells supernatants. These data suggest that the inhibitory effects are secondary to interaction of the antiserum with B cells determinants.

B-Lymphocytes↗
PubMed1984

A case of rheumatoid nodule formation within the central nervous system and review of the literature.

We describe nodule formation within the central nervous system (CNS) in a patient with seropositive rheumatoid arthritis (RA). Review of 13 previous reports of CNS rheumatoid nodule formation suggests that the clinical course is usually one of longstanding seropositive disease. Correlation of neurologic signs and symptoms with anatomic lesions has frequently been tenuous. We conclude that CNS nodules are a rare extraarticular feature of RA which, although often of uncertain clinical significance, should be considered as a possible etiology when neurologic dysfunction occurs in the RA patient.

Arthritis, Rheumatoid↗
PubMed1980

Hapten-specific human T cell lines. I. Functional analysis with respect to cytotoxic and helper activity.

Human PBL cells, sensitized in vitro to TNP or FITC-modified autologous stimulators, have been successfully grown in long-term culture by using TCGF derived from PHA-activated tonsil cells. Long-term cultures consist almost exclusively of T lymphocytes as defined by the formation of spontaneous rosettes with sheep erythrocytes and C-mediated lysis with heteroantibodies to human T cells (R alpha T H). The majority, but not all of these T cells, bear surface Ia antigens as detected by C-mediated lysis in the presence of alpha p23,30. Functionally, these cultures maintain high levels of hapten-specific cytolytic activity during many weeks of culture. In addition, a number of these T cell lines exhibit hapten specific proliferation when co-cultured with x-irradiated hapten modified autologous cells. During this proliferative response, helper factor(s) are released that trigger B cell differentiation into AFC. Data are presented that demonstrate that helper factor(s) production by T cell line cells is preferentially triggered by autologous, but nt allogeneic stimulator cells, bearing the relevant hapten.

Animals↗