ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb03180.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb03181.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb03182.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

In order to define whether CD4+T cells from autoimmune and non‐autoimmune thyroid tissue could be classified according to their mediator production, lymphokine production was studied in 63 thyroid‐derived CD4+T‐cell clones from four patients with Graves’disease, one with Hashimoto's thyroiditis, and one with non‐toxic goitre (9‐12 clones per patient). The production of interleukin 2 (IL‐2). gamma interferon (IFN‐γ), tumour necrosis factor alpha(TNF‐α). lymphotoxin(LT), interleukin 6 (IL‐6) and transforming growth Factorβ(TGF‐β) was assessed at the mRNA level by slot‐blot analysis in unstimulated clones as well as after activation with monoclonal anti‐CD3 (OKT3) and IL‐2 No lymphokine production was found in unstimulated clones, whereas 56% of the clones produced all six lymphokines simultaneously after stimuilation. In the remaining 44% usually not more than one lymphokine was missing from the complete panel Lymphokine mRNA concentrations varied between different clones and different patients, but. in this small sample, not between the diseases from which the clones were originated. There‐was a significant correlation between IL‐6.LT, and IL‐2 mRNA levels and T‐cell helper function. which was estimated by the stimulation of thyroid microsomal autoantibody production using autologous peripheral B cells. TGF‐β(and IFN‐γmRNA expression was unrelated to T‐cell help. The results demonstrate that intrathyroid T cells from autoimmune and non‐autoimmune thyroid disorders cannot be classified according to their lymphokine production, unlike some results with in vitro‐induced mouse T‐cell clones, where two populations. Th1 and Th2, have been described. SingleT cells are capable of producing a whole panel of lymphokines and thus are cap

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb03183.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

In this paper data are presented indicating that immunotherapy with monoclonal anti‐idiotypic antibodies (MoAb anti‐id) can provoke different responses in the B‐cell tumour concerned. With respect to the course of disease during and after immunotherapy, the in vitro findings may very well explain the in vivo observations in the two patients (D.E.F. B.O.R.) with B‐cell chronic lymphocytic leukaemia (B‐CLL) who were treated with MoAb anti‐id. After initial tumour reduction, there was a recurrence of tumour cells with altered functional and phenotypic properties. In both cases the recurring tumour cells still expressed the same idiotype.In one patient (D.E.F.) the phenotypic changes (a surface Ig change from IgM, IgG, IgA, and IgD to weakly positive IgM and IgD) and functional changes (a 10‐fold increase in [3H]thymidine uptake and a decreased idiotype secretion in vitro), together with the in vivo findings with respect to the course of disease–at relapse an impressive tumour regrowth rate with constant serum idiotype level–suggest that immunoselection might have taken place favouring the survival and relapse of a less mature, more aggressive tumour cell population with a lower idiotype expression.In the second patient (B.O.R.), the phenotypic changes (an isotype change from IgM and IgD to IgM with the loss of IgD, and a gradual decrease in expression of CD 19 and CD24) and functional changes (a 10‐fold increase of idiotype secretion in vitro), together with the in vivo finding that the serum idiotype level had increased 25‐fold compared with the preimmunotherapy serum level with comparable tumour load, strongly suggest an immunotherapy‐induced differentiation of the malignant B cell.We also describe an increased expression of CD74, detected by MoAb BoM22, on the recurring tumour cells of patient B.O.R. whereas the expression of HLA‐DP, ‐DQ and ‐DR did not change. The significan

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb03184.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Previous studies have shown that in vitro stimulation of human B lymphocytes with antigens such as ovalbumin (OA) induces the Formation of small antigen‐specific plaque‐forming cells (PFC) but precludes the activation of the B cells into full‐blown antibody‐secreting cells insufficient production of T cell‐derived growth and differentiation factors appears to be the basis of the phenomenon. Furthermore, cord blood B lymphocytes required 100 limes less OA to become activated in vitro into antigen‐specific PFC, and the distinct antigen‐handling capacities of neonatal monocytes are the basis of this result. We have studied the role of interleukin 1 (IL‐1) in the in vitro response of B lymphocytes from either cord blood or adult blood to OA. Addition of IL‐1 to the B‐cell cultures significantly increased the number of PFC. and about 50% of the plaques now appeared to be high‐rate IgM anti‐OA secreting PFC. The IL‐1 ‐mediated increase in the PFC response was shown to be based on potentiation of T‐helper cell activity. The differences between cord blood and adult blood mononuclear cells in the optimal OA concentration required for effective in vitro activation of B cells remained the same upon addition of II‐1 This result shows that the ph

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb03185.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

We have attempted to investigate the relative roles of specific cytotoxic T lymphocytes (CTL) and allospecific suppressor T cells (T5) in the systemic and intestinal manifestations of acute graft‐versus‐host reaction (GvHR) in mice.Treatment adult (C57Bl/10xDBA/2)F1(BDF1) mice with the suppressor cell‐specific toxin 2'‐deoxyguanosine (dGuo) inhibited the weight loss and mortality which normally occur after induction of GvHR and C57BI donor cells. dGuo also delayed the development of a destructive enteropathy as typified by jejunal villus atrophy. Paradoxically, dGuo completely prevented villus atrophy during an acute GvHR in neonatal (CBA × BALB/c)F1hosts, despite having only a slight ability to inhibit the systemic disease. In both models. dGuo had no effect on the generation of splenomegaly or anti‐host CTL. and dGuo‐treated mice with GvHR actually had increased proliferative alterations in the intestine, as assessed by crypt hyperplasia, In parallel. dGuo prevented the loss of NK cells which normally occurs in acute GvHR.Thus dGuo inhibits many of the destructive features of systemic and intestinal GvHR without affecting the development of CTL. We conclude that a dGuo‐sensitive mechanism causes the transition from a proliferative to a de

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb03186.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The cytolytic effects of natural killer (NK) cells have been extensively studied in recent years. In the present study we have investigated the cytostatic effects of SK cells Human peripheral blood lymphocytes from healthy volunteers were used as a source of effector cells, and the cell lines K562, U937, U1285, and Molt‐4 were used as target cells Effector cells were enriched for NK cells Using Percoll gradients and depleted of NK cells on Percoll gradients or by using Leu‐19 antibodies and magnetic heads. By monitoring cell numbers during co‐culture of effector cells and K562, it was found that after an initial phase of cell killing for 3 h target cell numbers remained stable during the following 24‐48h. In a microcytotoxicity assay measuring inhibition of uptake of [3H]thymidine, the four target cell types were shown to have different NK sensitivity; inhibition of ≥ 80% was obtained for K562 and U937 at an effector to target cell (E/T) ratio of 30:1, 50% for U1285, and 30% for Molt‐4. This inhibition was shown to be partly a direct effect on DNA synthesis for all cell lines, as Incorporation of [3H]thymidine was decreased in co‐cultured target cells compared with an equal number of target cells alone. Inhibition of DNA synthesis was thus not directly related to cell death and was also observed for the Molt‐4 cell line‐that was not killed. A cell division assay, with target cells m agarose and effector cells m a liquid tippet layer, showed a decline in the rate of target cell divisions Effects on the cell cycle were studied on latent‐phase cells. It was shown that effector cells delayed the onset of DNA synthesis This anti‐proliferative effect was observed for several days, but cell growth then gradually resumed the effector cells were identified as CD56‐positive large granular lymphocytes (I. GL). Double‐layer cultures and experiments using effector cell supernatants demonstrated that the growth‐inhibitory effect could be mediated by soluble factors, and the production of such factors was stimulated by exposure to a small proportion of target cells (50:1), Studies with specific antibodies indicated that growth inhibition was not mediated by alpha interferon (IFN‐α) but it was partly mediated by tumour necrosis factor alpha (TNF‐α). It is concluded that NK cells have a growth‐inhibitory effect that is distinct from the cytolytic effect and this activity is probably mediated by seve

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb03187.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Five heterogeneous IgA‐immunodeficient patients were analysed for expression of the α‐chain gene. The number of surface IgA‐bearing B cells was low in four patients Southern blot analysis indicated no deletion of immunoglobulin structural genes coding for Cα or α switching‐region genes. The number of surface IgM and IgA double‐bearing B cells increased in some patients. Addition of recombinant tnterieukin 4 (rIL‐4). rIL.‐5. and rIL‐6 to the normal B cells enhanced IgA production. However. B cells of the patients showed no or one‐third lower IgA production in response to these lymphokines, even though there was proliferation ill 4, rIL ‐5, and rIL‐6 induced low or no expression of α mRNA of the patients B cells These results suggested that the patients lacked B cells able to produce transcripts for the IgA heavy chain, and that some patients’B cells might be defective at the switch‐recombination process from u to a or fro

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb03188.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

A minor population of T cells expresses a heterodimeric antigen receptor composed of y andAchains (TcR‐1). In blood from adults, two subsets of Tγδ cells can be identified by the monoclonalantibodies (MoAb) BB3 and A13. Little is known about the distribution and markers of these subsets early in life. We have therefore examined both the frequencies of these cells in cord blood and their expression of the cytotoxicity‐associated marker serine esterase (SK). using immunocytochemical techniques.Our data show lower percentages of TcR‐1+cells in the blood of newborns compared with that in adults. However, the ratio of the Al3+/BB3 cells was significantly higher in cord than in adult blood. Whereas virtually all the adult TcR‐1+cells in blood were SE‐positive. only a small proportion of the cord blood cells earned ibis enzymes. This was; restricted lo the BB3+Tγδ ‐cell subset in the cord.Our data suggest different characteristics of the TcR‐1+cells in blood from newborns compared with adult blood, and study of the functions of the different subsets, e.g. cytotoxicity. will be important in understanding their particular

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb03189.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY