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L Chess

Publications and source records attributed to L Chess.

At least 55 records · Page 3Linked to original sources
PubMed1983

Relationship between human T cell functional heterogeneity and human T cell surface molecules.

Our knowledge of human T cell differentiation and function has expotentially increased during recent years. With this growth in knowledge there has been an increase in our appreciation of the complexity of the T-T interactions which initiate and control immune responses. A great deal remains to be learned concerning the mechanisms of these complex cellular interactions. In particular, it will be important to precisely understand the clear heterogeneity of functions within isolated subsets of OKT4+ and OKT8+ T cells. Perhaps, as importantly, it will be necessary to define more clearly the functions of the T4 and T8 molecules as well as the precise function of the other defined glycoproteins on the T cell surface. The evidence is clearly emerging that many of those molecules are not solely markers of unique functional subsets and are intimately involved in the functions of T cells.

Animals↗
PubMed1983

Functional subsets of human monocytes defined by monoclonal antibodies: a distinct subset of monocytes contains the cells capable of inducing the autologous mixed lymphocyte culture.

The induction of most immune responses requires the close cooperation between T cells and antigen-presenting cells (APC), presumably of monocyte/macrophage (M phi) lineage. To characterize human APC further, we used two monoclonal antibodies, OKM1 and OKM5, to isolate and identify M phi subsets. OKM1 has been described and recognizes cell surface antigens on most M phi and granulocytes. OKM5 recognizes cell surface determinants present on the majority of human M phi but does not recognize other hematopoietic cell types. A small subset of peripheral blood M phi is OKM1-OKM5+. Human peripheral blood E- cells were separated into OKM1+ and OKM1- subsets by a rosetting technique utilizing anti-Ig-coated red cells. The capacity to present self antigens in the autologous mixed lymphocyte culture (AMLC) resided predominantly within the E-OKM1- subset, even if surface membrane Ig-positive cells were eliminated. Similar experiments showed that the ability to stimulate in AMLC was contained in the E-OKM5+ population and in fact resided primarily within the E-OKM1-OKM5+ subset. All of these subsets were able to trigger allogeneic T cells to proliferate. The capacity of these APC subsets to present soluble antigens (mumps, tetanus toxoid) was also examined. The data demonstrated that although the majority of these APC are E-OKM1+, E-OKM1-OKM5+ cells can also present foreign antigen. Taken together, these data suggest OKM1 and OKM5 can be used to isolate two functionally distinct human M phi subsets. One subset (E-OKM1+) is capable of presenting soluble antigens but shows minimal ability to trigger AMLC. The other subset (E-OKM1-OKM5+) can also present soluble antigens but is the predominant subset that can trigger AMLC.

Animals↗
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↗
PubMed1982

Phenotypic heterogeneity of human T-cell malignancies: demonstration by monoclonal antibodies and cytochemical markers.

The present study sought to delineate the phenotypic heterogeneity of the human T-cell malignancies. Twenty T-cell neoplasms were investigated for reactivity with the OKT hybridoma monoclonal antibodies and expression of acid alpha-naphthyl acetate esterase (ANAE), beta-glucuronidase (BG), and acid phosphatase (AP) activity. Twelve cases (Mycosis fungoides, Sezary syndrome, cutaneous T-cell lymphoma, chronic lymphocytic leukemia) were OKT3'T4', ie, expressed the phenotype commonly associated with mature T-helper cells. These cases were further divisible into ANAE+BG+ (6 cases), ANAE-BG+ (5 cases), and ANAE-BG- (1 case) phenotypes. In contrast to the 12 OKT3+T4+ cases, the remaining 8 cases showed considerable inter- and intratumor heterogeneity with respect to reactivity with the OKT antibodies. Six of these cases (acute lymphoblastic leukemia, lymphoblastic lymphoma) expressed phenotypes consistent with various intrathymic stages of T-cell differentiation. Five of the latter 6 cases were AP+BG+ANAE-, analogous to the majority of normal cortical thymocytes; an OKT3+T4-T8+T10+ neoplasm was ANAE+, analogous to normal medullary thymocytes. Two cases expressed the previously undescribed OKT3+T4-T8-T10+ phenotype. These studies demonstrate that the T-cell malignancies are divisible into phenotypes which correspond to normal maturational stages of T-cell differentiation and functionally distinct T-cell subsets. Phenotypic analysis of the human T-cell malignancies may provide a basis for understanding their biological heterogeneity and may aid in the identification of transitional stages of T-cell differentiation and minor T-cell subsets.

Adolescent↗
PubMed1982

Further dissection of the functional heterogeneity within the OKT4+ and OKT8+ human T cell subsets.

Previous studies have suggested functional heterogeneity within the OKT4+ and the OKT8+ populations. For example, after activation the OKT4+ population contains not only helper cells but also cells capable of suppressing B cell differentiation. Previous studies also indicate that the reciprocal T cell population, OKT8+, does not provide helper activity but contains cytotoxic effector cells and radiosensitive cells important in the suppression of B cell differentiation. Using a new differentiation antigen, OKT17, which recognizes a surface antigen present on the majority of resting normal peripheral T lymphocytes but is present only on a subset of OKT4+ cells after activation, evidence was obtained that two functionally mature subsets can be distinguished within the OKT4+ population itself: OKT4+17+ radiosensitive suppressor cells and OKT4+17- radiosensitive helper cells. Recently, another monoclonal antibody, OKT20, has been described which is present on a small percentage of resting lymphocytes but is expressed in varying proportions on activated T cells. Functional analysis of normal resting human T lymphocytes demonstrated that the OKT20-depleted T cell subset was able to generate cytotoxic cells and to suppress antibody production to the same extent as did OKT8+ cells. On the other hand, when unselected T lymphocytes were cultured for six days in a mixed lymphocyte reaction and then depleted of OKT20 reactive cells, the cytotoxic effector T cells were eliminated. In contrast, OKT20-depleted T cells after identical activation were still able to suppress antibody production. These data provide evidence that following activation of OKT8+ cells, the OKT20 differentiation antigen becomes selectively expressed on cytotoxic effectors but not on suppressor cells.

Antibodies, Monoclonal↗
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↗
PubMed1981

Generation of functional human T cell hybrids.

Human T cell hybrids were generated by fusing lectin-activated normal and leukemic human T cells with an aminopterin-sensitive human T cell line. This mutant cell line, designated CEM-T15, was derived from the human T cell line CEM after chemical mutagenesis with ethane methylsulfonate and subsequent culture in medium containing 6-thioguanine. After polyethylene glycol-induced fusion, the cells were cultured in hypoxanthine-aminopterin-thymidine selective medium. More than 5 wk after fusion, evidence for successful hybridization was obtained by three independent criteria: (a) The majority of the cultures contained cells expressing the OKT3 surface antigen: this antigen is expressed on normal T cells but not on CEM-T15 cells. (b) Most of the cultures contained polyploid cells. (c) Some of the cultures provided helper activity in the generation of antibody-forming cells. This functional activity is absent from the CEM-T15 parental cell line. Evidence for functional stability of the hybrids greater than 20 wk after fusion was provided by several clones that not only continue growing exponentially but also maintain expression of OKT3 surface antigen and high levels of helper function. These T cell hybrids constructed using antigen-specific human T cells should be of considerable importance in further studies of the immunobiology of human T cells.

Aminopterin↗
PubMed1981

Functional analysis of human T cell subsets defined by monoclonal antibodies. IV. Induction of suppressor cells within the OKT4+ population.

In this report, we explored the functional heterogeneity within the OKT4+ subset of human T cells. Evidence was obtained that although in vitro pokeweed mitogen-activated OKT4+ cells can function as radioresistant helper cells, these activated OKT4+ cells could also exert potent feedback suppression. Despite the induction of suppressor cells after pokeweed mitogen activation, the OKT4+ population maintains its original OKT3+, OKT4+, nd OKT8- surface phenotype. The suppressor cells contained within the activated OKT4+ population were found to be radiosensitive. Importantly, the suppression mediated by activated OKT4+ cells required the presence of radiosensitive cells contained within the resting OKT4+ population. Taken together, these results suggest that the OKT4+ subset of human T cells contains cells that can be activated to differentiate into suppressor cells independent of OKT8+ cells.

Antibodies↗
PubMed1981

Plasma cell dyscrasia and peripheral neuropathy: identification of the myelin antigens that react with human paraproteins.

In some cases of polyneuropathy and plasma cell dyscrasia, the monclonal antibodies react with human peripheral nerve myelin. To identify the myelin antigens involved, we separated the proteins of human central and peripheral nerve myelin by polyacrylamide gel electrophoresis, transferred the proteins onto nitrocellulose sheets, and used an immunoenzymatic technique to detect the reactive antigens. Serum IgM but not IgG from three patients with neuropathy and complement-fixing anti-human myelin IgM paraproteins immunostained a protein of approximately 100,000 daltons in human peripheral nerve myelin and a protein or closely migrating proteins of similar size in human central nervous system myelin. In a fourth patient, both IgM and IgG immunostained the antigen. Immunostaining was specific for the paraprotein light chain type, and absorption of the patients' sera with human peripheral nerve myelin eliminated the reaction with the central nervous system proteins. No reaction was seen with rabbit peripheral nerve myelin or with membranes prepared from human myotubes, human T cells, or human fibroblasts. Control sera from six patients with neuropathy and IgM paraproteins that did not react with myelin, from four patients with IgM paraproteins but no neuropathy, and from three normal subjects did not immunostain myelin.

Antibodies, Monoclonal↗
PubMed1981

Dissection of distinct human immunoregulatory T-cell subsets by a monoclonal antibody recognizing a cell surface antigen with wide tissue distribution.

A monoclonal antibody, PVR-11, was obtained after hybridization of X63Ag8.653 murine myeloma cells with spleen cells from a mouse immunized with human lymphocytes. It recognizes a 175,000- to 185,000-dalton surface antigen present on approximately 80% of normal human peripheral T lymphocytes, 50% of non-T non-B cells, and less than 10% of B cells as determined by complement-dependent microcytotoxicity. It is also present on various leukemia T cells, on some but not all T lymphoblastoid cell lines, and on a small fraction of some B lymphoblastoid cell lines. Some B-cell chronic lymphocytic leukemia cells also express the PVR-11 antigen. Functional analysis of normal human T lymphocytes demonstrated that the PVR-11-depleted T-cell subset contains the precursors of both cytotoxic and suppressor cells but lacks helper cells. On the other hand, cytotoxic effector T cells express the PVR-11 antigen. These results demonstrate that antigenic determinants with relatively wide tissue distribution can dissect functionally distinct human immunoregulatory T-cell subsets.

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↗
PubMed1981

Functional analysis of human T cell subsets defined by monoclonal antibodies. II. Collaborative T-T interactions in the generation of TNP-altered-self-reactive cytotoxic T lymphocytes.

In previous reports we have demonstrated that human T cells, responding to soluble and alloantigens, release helper factor(s) that amplify primary in vitro hapten-altered-self-reactive CTL responses. In the present studies, we have employed complement-fixing monoclonal antibodies (OKT4 and OKT8) that recognize functionally distinct human T cell subsets to investigate the role of T-T interaction in the generation of these killer cells. In all experiments, purified OKT4+ responder T cells were deficient in cytotoxic activity, whereas responder populations containing OKT8+ T cells generated substantial cytotoxicity; demonstrating that TNP-altered-self-reactive CTL precursors are contained within the OKT8+ T cell subset. Further, optimal cytotoxic responses were obtained from responder populations containing both OKT4+ and OKT8+ T cells, suggesting that cooperative interaction between these subsets may result in an amplification of killer cell activity. This interpretation was supported by the following observations: (1) the amplifying effect of soluble antigen required the presence of both OKT4+ and OKT8+ responders; (2) during MLC, OKT4+ but not OKT8+ responder T cells generate helper factor(s) that amplify TNP-altered-self-reactive CTL responses; (3) helper factor(s) bypass the requirement for direct OKT4-OKT8 T cell interaction, triggering a CTL response that is proportional to the percentage of OKT8+ T cells present within the responder population. In additional studies, we determined that the TNP-altered-self-reactive effector CTL maintain the OKT3+, OKT4-, OKT8+ surface phenotype displayed by the CTL precursor.

Antibodies↗
PubMed1980

High molecular weight antigens present on human T cells.

A series of eight high molecular weight (140,000-220,000) glycoproteins on human peripheral T cells were recognized by radioimmunoprecipitation with a rabbit antiserum. The pattern of antigens present on each of eight human T cell lines studied was unique, and no line displayed the range of antigens present on peripheral T cells. The pattern of bands on peripheral T cells changed after allogeneic or lectin stimulation. Adsorption/elution experiments with antiserum showed that some of these proteins were antigenically related, and at least three different groups of proteins were present. Two of these groups could be partially distinguished by their ability to bind to ricin or lentil lectin and by their reactivity with two additional rabbit antisera. On some cell lines, it was found that proteins bound by lentil lectin but not ricin were precursors of higher molecular weight material recognized by ricin. Taken together, the data suggest that these proteins may be the products of a multigenic or multiallelic system, probably equivalent to the murine Ly 5 antigens.

Antigens, Surface↗
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↗
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↗