摘要:

AbstractA mouse T cell hybrid specific for pigeon cytochromecin the context of I‐Ekresponds by secreting interleukin 2 when co‐cultured with the native antigen and the B cell lymphoma, LK‐35.2, or naive splenic B cells as antigen‐presenting cells (APC). Cytochromescand their corresponding C‐terminal fragments which are not capable of stimulating the TPc9.1 cells, including the autologous mouse cytochromec, block the T cells' response to pigeon cytochromec.In contrast, nonstimulatory N‐terminal peptides of cytochromec, which share no homology with the antigenic peptide, do not block. Blocking is observed when the nonstimulatory cytochromescor peptides are present in culture with the live APC and nonsaturating concentrations of pigeon cytochromec. it can be overcome with supraoptimal concentrations of pigeon cytochrome c. With tobacco hornworm moth cytochromecas antigen, a protein for which the T cell has a higher functional affinity, the response of TPc9.1 cannot be blocked by the nonstimulatory cytochromescor by peptides, even when limiting concentrations of the tobacco hornworm moth cytochromecare used. When paraformal‐dehyde‐fixed APC are employed, no native cytochrome c can stimulate the T cells, including the tobacco hornworm moth protein which with the live APC is effective at 50 to 100‐fold lower concentrations than pigeon cytochrome c. However, with fixed APC the T cells are stimulated by the C‐terminal fragments containing residues 81‐ 104 of the pigeon protein or residues 81‐103 of the tobacco hornworm moth protein as readily and with the same relative efficiencies as the native protein, presented by live APC. The nonstimulatory peptides, but not the native cytochromesc, block T cell activation by pigeon cytochromecpulsed‐fixed APC, indicating that the nonstimulatory peptides compete with the stimulatory pigeon cytochromecpeptides produced by the APC. This competition appears to be due to nonstimulatory peptides which associate at the APC surface and not to those acting from solution because the APC which have been incubated with pigeon cytochromecand nonstimulatory peptides and washed free of excess antigen and peptides are not stimulatory to the T cell hybrid. It was concluded that the activation of a pigeon cytochromec‐specific T cell, which recognizes a peptide fragment of the native protein on the surface of an APC, can be blocked by an excess of nonstimulatory homologous peptides when these are also associated on the surface of the APC. The ability to block T cell activation does not appear to be competition for processing of the native molecule but may represent a competition for specific peptide binding sites on the AP

ISSN:0014-2980    

DOI:10.1002/eji.1830160702

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractA murine monoclonal antibody (mAb) specific for apocytochromecwas found to be able to either inhibit or enhance the helper activity of mouse apocytochromec‐specific T cell clones and populations in a hapten (trinitropheny1)‐carrier (apocytochromec) system of T‐B cell cooperation. This effect of the mAb was carrier specific, could not be ascribed simply to a shift in the kinetics of the antibody response and was observed using apocytochromecT helper cells of different mouse haplotypes. In addition, the anti‐apocytochromecmAb was able to inhibit specific T helper cell activity even when the T cells were triggered with antigen‐presenting cells pulsed with antigen. Taken together, these results suggested that the mAb was inhibiting helper activity due to its ability to modify the interaction between T cells and antigen‐ prese

ISSN:0014-2980    

DOI:10.1002/eji.1830160703

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractInterferons (IFN) have been shown to modulate the expression of a number of cell surface antigens on macrophages and lymphocytes. Because such phenotypic alterations may be involved in the functional effects of IFN, it appears important to characterize further these alterations. In the present work, we evaluated the response to IFN of Ly‐6‐encoded molecules on murine T cells. Two types of Ly‐6 antigens, Ly‐6A and Ly‐6C, normally present on minor subsets of mature T cells were studied. It was found thatinvivotreatment of mice with the IFN inducer poly(I.C) or with purified IFN‐α/β resulted two days later in augmented expression of these antigens. Purified T cells culturedin vitrofor 2 days in the presence of 5% serum from poly(I.C)‐treated mice or of lo4units/ml IFN‐α/β also displayed dramatically increased (4‐12‐fold) amounts of Ly‐6 antigens. Under the same conditions, the T cell markers Thy‐1, Ly‐1, Lyt‐2 and MT4 were unaffected or slightly diminished while surface expression of H‐2 or β2‐microglobulin antigens was increased by only 10‐36%. Therefore, poly(1. C)‐ induced or purified IFN interacts with resting T cells to selectively enhance Ly‐6 antigen expression. This phenomenon was found to correlate functionally with increased proliferative response of the T cells, in presence of phorbol myristate acetate, to anti‐Ly‐6 antibodies cross‐linked on their surface. Enhancement of Ly‐6 antigen expression on T cells may

ISSN:0014-2980    

DOI:10.1002/eji.1830160704

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractA monoclonal antibody (CB.1) is described that defines a new triggering signal for human cytotoxic T lymphocytes (CTL). The antibody precipitates a 103‐kDa surface antigen from activated normal human T cells. The antigen is undetectable or present in only low amounts on resting T lymphocytes but its expression increases strongly after activation and proliferation on T4+and T8+T lymphocytes. Binding of antibody CB.1 to CTL results in triggering of the lethal hit. This induction of cytotoxicity is dependent on cross‐linking of CTL and an Fc receptor‐bearing target cell with CB.1 and requires Ca2+like antigen‐specific triggering. CB.1‐induced triggering can be specifically inhibited by binding of antibodies to the T8 or T4 molecules on T8+

ISSN:0014-2980    

DOI:10.1002/eji.1830160705

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractIn order to determine whether or not the major histocompatibility complex (MHC)‐ encoded restriction element used by a T cell in the recognition of its primary antigen affected its ability to be cross‐reactively stimulated by MAS (a soluble product ofMycoplasma arthritidis), a panel of cloned, soluble antigen‐specific I‐A‐ and I‐E‐ restricted T cells were tested for their ability to cross‐reactively recognize and respond to MAS. Initial studies indicated that all of the cloned T cells tested were capable of responding to MAS in the presence of genetically EαEβ‐expressing (I‐E+), but not EαEβ‐non‐expressing (I‐E‐) accessory cells (AC). However, subsequent studies demonstrated that the ability of most of these T cell clones to mount proliferative responses to MAS in the presence of I‐E+AC was dependent upon the presence of Lyt‐1+2−T cells in the irradiated spleen cells which were used as AC sources. When T cell‐depleted, I‐E+populations of spleen cells or an I‐E+antigen‐presenting line (WEHI‐5) were used as AC sources, only 6 of the 34 clones tested were found to be directly responsive to MAS. Subsequent to stimulation by MAS plus I‐E product, these MAS‐reactive T cell clones were capable of “recruiting” bystander T cells to proliferate. Finally, the ability of a given T cell clone to respond to MAS plus I‐E product did not appear to be influenced by the restriction element used by that clone in its response to other antigens since both I‐A‐restricted and I‐E‐restricted T cell clones were responsive to MAS plus I‐E in equivalent proportions. Thus, the data presented indicate that I‐E‐restricted T cell reactivity to MAS is a clonally expressed property of T cells that is independent o

ISSN:0014-2980    

DOI:10.1002/eji.1830160706

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractSpontaneous AKR leukemias express murine leukemia virus (MuLV)gagandenvgene‐encoded structural proteins on their cell surface. Cytotoxic T lymphocytes (CTL) induced in AKR mice by syngeneic leukemia 369 which expressed high amounts of H‐2 antigens recognized viral gag polyproteins in association with H‐2K antigens as target antigens. H‐2K‐negative leukemias were resistant to lysis by AKR/ Gross MuLV‐specific CTL and did not induce a cellular immune response. However, they became susceptible after stimulation with interferon. H‐2K‐positive leukemias induced CTL which were cytotoxic for 369 cells. However, the majority of H‐2K‐ positive leukemias was not lysed by CTL induced by autologous immunization. These leukemias were also resistant to lysis by anti‐369 CTL, but could restimulate AKR/ Gross‐specific CTLin vitro, and were susceptible to lysis by H‐2Kk‐ restricted CTL against AKR minor histocompatibility antigens. Thus, there could be specific defects of the H‐2Kkantigens of these tumors. However, there were also qualitative and quantitative differences in antigenic determinants of the gag targe

ISSN:0014-2980    

DOI:10.1002/eji.1830160707

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractHuman B lymphocytes preactivated withStaphylococcus aureusCowan strain I can proliferate and differentiate to Ig‐secreting cells when cultured in the presence of recombinant interleukin 2 (IL2). We have compared 2 different B cell growth factors (BCGF) and a B cell differentiation factor (BCDF) to IL2 in the regulation of human B lymphocyte growth and differentiation. Utilizing a competitive binding assay, neither a high molecular weight BCGF (HMW‐BCGF) nor a low molecular weight BCGF (LMW‐BCGF) competitively inhibited the binding of radiolabeled IL2. Blocking studies with the anti‐Tac monoclonal antibody demonstrated that B cell proliferation to IL2 was inhibited while a crude supernatant containing BCGF and IL2 was only partially inhibited. B cell Ig secretion induced by IL2 was also inhibited by anti‐Tac while a crude supernatant and partially purified BCDF were not. Furthermore, IL2 plus BCGF was shown to enhance B cell proliferation better than either factor alone and IL2 plus a BCDF enhanced B cell Ig secretion better than either factor alone. By separating activated B cells into Tac‐positive and Tac‐negative fractions, much of the previously noted enhancement with the 2 factors was found to be secondary to the differential sensitivity of the 2 populations to BCGF and IL2 or BCDF and IL2. Thus, LMW‐BCGF, HMW‐BCGF and a partially purified BCDF appear to interact with receptors distinct from the IL2 receptor in mediating their effects on B cell growth an

ISSN:0014-2980    

DOI:10.1002/eji.1830160708

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractHuman T cell clones which were able to proliferate in response to specific stimuli but could not kill even in the presence of lectins were found to acquire the specific lytic function when interferon alpha or gamma was added on day 1 of the 7‐day restimulation culture. These results demonstrate that interferon may act as a cytotoxic T lymphocyte differentiation signal. This signal can be blocked by the monoclonal antibody LeoA1 which recognizes a 70‐kDa cell surface structure, involved in cytotoxic T lymphocyte differentiat

ISSN:0014-2980    

DOI:10.1002/eji.1830160709

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractUsing light scatter, flow cytometric and functional analyses, three major stages in thein vitroactivation of human thymocytes were defined. The earliest stage (day 0–2) was characterized by the induction of the interleukin 2 (IL2) and transferrin receptors, the T cell lineage specific Tal antigen, and increased reactivity with anti‐T8 antibody. At this time, major changes in nuclear morphology but not cell size were observed. Early‐stage thymocytes were immature with regard to T3 and cytotoxic capacities. The second stage (day 3–4) ofin vitroculture was distinguished by loss of T6, maximal activation (both in cell size and nuclear morphology) and maximal expression of both transferrin and IL2 receptors. At this stage, nearly all thymocytes expressed T3, 30–70% of thymocytes were T4+T8+, and functionally, only small increases in cytotoxic capacities were observed. The third stage of maturation (day 5–7) represented thymocytes with reduced levels of activation as measured by forward and right angle light scatter analysis and declining IL 2 and transferrin receptor expression. However, these thymocytes exhibited high levels of T3 antigen density, loss of T4, T8 coexpression and pronounced cytotoxic and detectable inducer function c

ISSN:0014-2980    

DOI:10.1002/eji.1830160710

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY

摘要:

AbstractA recently described long‐term culture system offers a unique experimental approach for dissecting regulatory mechanisms that control the developmental progression of B‐lineage lymphocytes. Lymphoid cells, including B cells and their precursors, can be maintained for prolonged periods in strict dependence on a layer of adherent cells. However, before this system can yield to interpretable manipulation, much information is needed as to the identity and temporal phenotypic stability of both lymphoid and nonlymphoid cells. The findings reported here provide answers to some of those important questions. Successful establishment of lymphoid cells in culture was extraordinarily dependent on the batch of fetal calf serum used in the medium, and some undesirable serum lots supported cultures that were virtually all myeloid. With standardized culture conditions, various populations of lymphoid cells were identified on the basis of B‐lineage differentiation markers and culture to culture variation was assessed. Lymphocytes that were firmly attached to the adherent cells were carefully compared to nonadherent lymphocytes in terms of cycle status, phenotype, size, and transferrin receptor expression. They were essentially identical in all of these respects and a partitioning of proliferating cells and their progeny in the cultures was therefore not apparent. It is also noteworthy that although a high mitotic rate was maintained, a majority of the cells were small lymphocytes. The outgrowth of identifiable B‐lineage cells (detected with monoclonal 14.8 antibodies) in replicate cultures was initially similar, but the extent of interculture variation increased dramatically during the period 4–6 weeks after initiation of culture. Replicate cultures established from the same marrow cell pool often differed as much as 20‐fold in numbers of 14.8‐positive cells. After this time, the composition of individual cultures evolved much more gradually, and numbers of B cells and pre‐B cells remained relatively constant. This indicates that subsets of lymphocytes become established in each culture dish during a discrete phase.At least two types of supporting adherent cells predominated in these cultures: typical macrophages and very large, nonphagocytic cells resembling adventitial reticular cells. The latter included subpopulations resolved on the basis of alkaline phosphatase content. In contrast to the lymphoid populations, proportions of these adherent cell types were relatively invariant among replicate cultures. The dramatic expansion or contraction of particular B‐lineage populations which occurred prior to 6 weeks of culture did not appear to be reflected in the composition of the adherent layers on wh

ISSN:0014-2980    

DOI:10.1002/eji.1830160711

出版商:WILEY‐VCH Verlag GmbH    

年代:1986

数据来源: WILEY