摘要:

AbstractWe established several H‐2‐restricted lymphocytic choriomeningitis virus (LCMV)‐specific cytotoxic T cell clones from spleens of virus‐primed C57BL/6 or C57BL/10 (H‐2b) and B10.BR (H‐2k) mice and from allogeneic C57BL/10→B10.BR and B10.BR→C57BL/10 bone marrow chimeras. Two T cell clones of H‐2borigin and restricted to H‐2b, 3 of H‐2korigin and restricted to H‐2kwere compared with two clones each derived from the two types of chimeras. Their surface phenotype was found to be Lyt‐2+, L3/T4−and KJ16‐133+(2 of 9). Clones from chimeras expressed bone marrow donor H‐2 and are restricted to the recipient H‐2.H‐2k‐restricted clones were all specific for Kkwhereas all H‐2b‐restricted clones were specific for Db. These restriction specificities could be further defined by the blocking activity of various monoclonal anti‐H‐2 antibodies. Interestingly the anti‐H‐2Dbantibodies blocked the restricted virus‐specific killing activity of the clones derived B10.BR→C57BL/10 chimeras much more effectively than the activity of the clones derived from conventional H‐2bmice.The various clones differed with respect to their fine specificity for LCMV strains. The 3 clones of conventional B10.BR origin only recognized LCMV‐WE but not LCMV‐Armstrong, Aggressive or Docile; H‐2b‐restricted conventional clones recognized target cells infected with all LCMV strains except LCMV‐UBC‐Docile; the T cell clones from the bone ma

ISSN:0014-2980    

DOI:10.1002/eji.1830170202

出版商:WILEY‐VCH Verlag GmbH    

年代:1987

数据来源: WILEY

摘要:

AbstractA chronic suppression of Igh‐1b and Igh‐3b (IgG2aand IgG2bof b haplotype) allotype expression has been induced by injecting T splenocytes from normal BALB/c or BC8 mice into newborn F1hybrids of appropriate Igh congenic strains: BALB/c into (BALB/c Igha× CB20 Ighb)F1and BC8 into (BC8 Igha× C57BL/6 Ighb)F1or (C57BL/6 × BC8)F1. This suppression does not affect IgM (Igh‐6b) or IgA (Igh‐2b) expression. When the Ighbhaplotype is paternally transmitted, the proportion of T splenocyte recipients showing allotypic suppression increases with time reaching 70% 40 weeks after birth. We also succeeded in inducing this pattern of suppression in 2 out of 13 cases when the Ighbwas inherited from the mother. These normal T splenocytes are therefore clearly allotype specific. As Igh‐6b production is not affected by the suppression, these T splenocytes are believed to influence B cells more or less committed to Igh‐1b or Igh‐3b production rather than more precocious Igh‐6b (IgM of b haplotype) carrying precursors in the classical IgM‐I

ISSN:0014-2980    

DOI:10.1002/eji.1830170203

出版商:WILEY‐VCH Verlag GmbH    

年代:1987

数据来源: WILEY

摘要:

AbstractThe functional activity of Moloney murine sarcoma virus (M‐MSV)‐specific T lymphocytesin vivowas assayed by the i.v. injection of virus‐specific T lymphocytes into T cell‐deficient “B mice”. Virus‐specific T lymphocytes generated in mixed lymphocyte tumor cell cultures were transferred i.v. into syngeneic “B mice” injected simultaneously at a distant site with the virus. These experiments indicated that a low dose (1 × 106cultured cells) of infused lymphocytes can afford protection. To define the T lymphocyte subpopulation which was active, Lyt‐2+lymphocytes were selected by “panning” on plastic petri dishes coated with anti‐Lyt‐2 monoclonal antibody, and Lyt‐2−lymphocytes selected by treatment with anti‐Lyt‐2 monoclonal antibody and complement. The results indicated that a Lyt‐2+lymphocyte‐enriched population was more efficient in conferring protection against M‐MSV‐induced tumors.To investigate if cytolytic T lymphocytes (CTL) alone had a protective effect, a M‐MSV‐specific CTL clone was transferred in the same model system. The results demonstrated that a M‐MSV‐specific CTL clone prevented M‐MSV‐induced tumor growth and also induced the destruction of syngeneic Moloney murine leukemia virus (M‐MuLV)‐induced MBL‐2 leukemic cells in the peritoneal cavity. However, the cell dose required to obtain protection using a CTL clone was higher than that which was effective when mixed lymphocyte tumor cell culture cells were used.To assess the ability of the transferred cells to home and to repopulate the lymphoid organs of the “B mice”, the frequency of virus‐specific CTL precursors in the spleen was evaluated by limiting dilution analysis. The results indicated that lymphocytes from mixed lymphocyte tumor cell cultures can be recovered from the spleens of “B mice” injected i.v. 25 days earlier. On the contrary, following the transfer of an active CTL clone, a very low frequency (<1/200000 cells) of virus‐specific CTL precursors was present in the spleens of recipient animals. The same M‐MSV‐specific CTL clone did not yield protection against M‐MSV‐i

ISSN:0014-2980    

DOI:10.1002/eji.1830170204

出版商:WILEY‐VCH Verlag GmbH    

年代:1987

数据来源: WILEY

摘要:

AbstractA monoclonal antibody (mAb) directed to a human leukocyte 55‐kDa cell surface molecule with identical cellular distribution and biochemical properties to the CD4 was able to inhibit T cell proliferation induced either in a mixed lymphocyte culture or by activation with mAb anti‐CD3, anti‐CD2 or phytohemagglutinin. The inhibitory effect of anti‐CD4 was observed in the absence of monocytes and was directly exerted on T4+cells.This effect on cellular proliferation appears to be due to an inhibition of a post‐activation event since (a) the rise of cytoplasmic Ca2+after activation with anti‐CD3 mAb is not affected by the presence of anti‐CD4 and (b) the proliferation that occurs after an activation pulse of 3 h with ionophore and phorbol myristate acetate can be inhibited when the anti‐CD4 is added after the pulse period. Kinetic studies demonstrated that the inhibition of cellular proliferation by anti‐CD4 mAb was observed even if the antibody was added as late as 18–24 h after the initiation of the culture. The effect of this blocking anti‐CD4 mAb on the interleukin (IL) 2/IL 2 receptor signalling pathways was also examined. The presence of anti‐CD4 slightly affected the production of IL 2. In fact, addition of exogenous recombinant IL 2 at the initiation of the cultures did not restore the proliferative response. However, anti‐CD4 had a strong inhibitory effect on the expression of IL 2 receptors as analyzed by direct immunofluorescence cytometry. Taken together, these results indicate that the binding of the anti‐CD4 mAb to T cells interferes with a late metabolic step being capable of abolishing the proliferative activi

ISSN:0014-2980    

DOI:10.1002/eji.1830170205

出版商:WILEY‐VCH Verlag GmbH    

年代:1987

数据来源: WILEY

摘要:

AbstractThis report describes the isolation, and the phenotypic and functional characterization ofPlasmodium falciparum‐specific human T lymphocyte clones (TLC) obtained from 2 acutely infected and 4 clinically immune donors. Approximately one third of the TLC obtained from the acutely infected patients had the phenotype CD8+/CD4−.No such clones were obtained from the clinically immune donors.P. falciparum‐specific, major histocompatibility complex‐restricted CD8+clones can lyse unrelated tumor cell targets in the presence of anti‐CD3 antibodies, suggesting that these clones have cytotoxic potential. Conversely no killing was obtained with two CD4+P. falciparum‐specific TLC, even in the presence of anti‐CD3 antibody. In addition the helper function of a CD4+clone was demonstrated in a T/B cell coope

ISSN:0014-2980    

DOI:10.1002/eji.1830170206

出版商:WILEY‐VCH Verlag GmbH    

年代:1987

数据来源: WILEY

摘要:

AbstractT lymphocyte clones specific for malarial (Plasmodium falciparum) blood stage antigens were obtained from acutely infected patients or from donors living in a malaria‐endemic area of West Africa. Thirty‐four clones carrying the CD4 antigen, and one CD8+clone, were tested in a proliferation assay for their capacity to recognizeP. falciparumisolates of different geographical origins. Only one clone distinguished between different parasite isolates (it failed to react with a parasite isolate originating from East Africa, but did recognize West African and Asian isolates). All of the clones responded well to intact erythrocytes containing viable parasites, but some responded poorly to extracts of parasitized cells. Eight of 19 clones studied (all CD4+) recognized parasite antigens which had characteristic mobilities in sodium dodecyl sulfate‐containing polyacrylamide gels. The antigens had apparent molecular weights of about 20000, 35000, 40000, 120000, 150000–200000 and 200000. These results (together with a previous report of two clones recognizing an antigen of molecular weight about 50 000, Sinigaglia and Pink,EMBO J.1985.4:3819) show that T cells in infected individuals react with at least 6 different parasite p

ISSN:0014-2980    

DOI:10.1002/eji.1830170207

出版商:WILEY‐VCH Verlag GmbH    

年代:1987

数据来源: WILEY

摘要:

AbstractIt has been shown that the activation of T cells by an anti‐idiotypic antibody (anti‐Id) TB71 containing an internal image of the corresponding mycobacterial antigen (38 kDa) was achieved by the interaction of anti‐Id TB71 with the T cell receptor complex (CD3/Ti). The accessory cell requirement in this response could not be replaced by anti‐Id TB71 coupled to Sepharose beads and was not inhibited by Fc receptor blockade. When taken together with the finding that anti‐Id TB71‐induced proliferation of a T cell clone was restricted by determinants encoded by the major histocompatibility complex, these findings suggested that anti‐Id TB71 was presented to 38‐kDa antigen‐reactive T cells by the same mechanisms as conventional antigenic determinants. That is, both stimulated T cells through the CD3/Ti complex and had to be presented in the context of class II molecules on accessory cells. The finding that the disruption of the integrity of the anti‐Id TB71 combining site did not affect T cell responsiveness although antibody binding was ablated implied that anti‐Id TB71 may be partially degraded and re‐expressed with MH

ISSN:0014-2980    

DOI:10.1002/eji.1830170208

出版商:WILEY‐VCH Verlag GmbH    

年代:1987

数据来源: WILEY

摘要:

AbstractThe effect of lipopolysaccharide (LPS) on the lymphokine (LK)‐dependent activation of murine peritoneal macrophages for intracellular killing ofLeishmania enriettiiparasites was investigated. Exposure to LPS alone did not induce macrophages to kill the parasite. In the presence of LK or recombinant interferon‐γ, however, which by themselves rendered the macrophages only weakly cytotoxic, considerable stimulation of intracellular parasite killing was achieved already at a LPS concentration of 1 ng/ml. The response to LPS was of the same magnitude in macrophages tested for intracellular killing as in parallel assays of extracellular cytolysis of target cells. Acquisition of leishmanicidal activity by macrophages exposed to LK and LPS correlated with stimulation of the respiratory burst, as shown by increased hexose monophosphate shunt levels, and priming for elevated chemiluminescence and O2−and H2O2production. Polymyxin B blocked both this LPS‐dependent metabolic activity and intracellular parasite destruction. Intracellular killing was, however, not solely dependent on oxidative metabolism of macrophages since (a) in the absence of LK, LPS stimulated respiratory burst activity, yet no intracellular killing was observed, and (b) triggering of the respiratory burst by phorbol myristate acetate or zymosan did not affect intracellular parasite survival. These results suggest that, in this experimental model, efficient intracellular parasite killing depends both on increased production of oxygen metabolites and on the availability of so far unidentified factor(s), the synthesis of which requires exposure of macrophages to both LK

ISSN:0014-2980    

DOI:10.1002/eji.1830170209

出版商:WILEY‐VCH Verlag GmbH    

年代:1987

数据来源: WILEY

摘要:

AbstractHigh density (resting) murine Lyt‐2+T cells exposedin vitroto the ligand concanavalin A (Con A) remain interleukin 2 (IL2) unresponsive,i.e.do not express functional IL2 receptors, unless reconstituted with accessory cells. This finding provides a bio‐assay to define functional and biochemical characteristics of an IL2 receptor‐inducing factor (RIF). RIF bioactivity as secreted from the macrophage cell line P388‐D1 is associated with a trypsin‐sensitive protein of 44 kDa which does not need to be glycosylated and which binds to and can be eluted from hydroxylapatite and phenyl‐Sepharose. While both RIF and IL1 are produced by accessory cells the lymphokines separate from each other according to functional and biochemical criteria.Either accessory cells, RIF or the protein kinase C activator phorbol myristate acetate can substitute for each other and are equally active for the induction of IL2 responsiveness in high‐density Lyt‐2+T cells exposed to Con A. To explain these results we conclude that in the mitogen system used, induction of IL2 responsiveness (activation) represents a two‐step event in which first cross‐linking of cell surface structures by the ligand Con A excites the responder T cells, which subsequently respond to the accesso

ISSN:0014-2980    

DOI:10.1002/eji.1830170210

出版商:WILEY‐VCH Verlag GmbH    

年代:1987

数据来源: WILEY

摘要:

AbstractIt is shown here that the C4‐77 and C4‐86 bone marrow clones with properties of pro‐T lymphocytes and the Bc/Bm 11 and CB/Bm7 clones with characteristics of pro‐B lymphocytes grow in recombinant interleukin 4 (rIL4)/BSF‐1 and IL3, but not in rIL2. The proliferative cell responses to rIL4/BSF‐1 were always less that ∼ 50% of those achieved by the clones in response to IL3. The CC11 monoclonal antibody (mAb) specific for IL3‐sensitive mouse cells did not affect the action of rIL4/BSF‐1, but it did inhibit the action of IL3 on the clones. The PC61 mAb against IL2 receptors had no effect on either rIL4/BSF‐1‐ or IL3‐driven responses. All four clones carry on the cell membrane the glycoproteins recognized by the CC11 mAb and by the PC61 mAb as assessed by immunofluorescence staining and flow cytometry. We conclude that the pro‐T and the pro‐B clones express functional receptors for IL3 and rIL4/BSF‐1 and nonfunctional receptors for IL2, that rIL4/BSF‐1 promotes growth of these clones via an IL3‐ and IL2‐independent pathway and discuss the possible biolog

ISSN:0014-2980    

DOI:10.1002/eji.1830170211

出版商:WILEY‐VCH Verlag GmbH    

年代:1987

数据来源: WILEY