摘要:

AbstractSeveral groups have described that a low percentage ofin vitrocultured T cell receptor (TcR) γ/δ cells express CD8. Contrary to TcR α/β cells, however, CD8 on these TcR γ/δ cells was shown to be a CD8α homodimer. We describe here that addition of interleukin‐7 (IL‐7) to a short‐termin vitroculture of fetal day 14 thymic lobes in an organ culture system or of fetal day 18 fetal thymocytes in cell suspension yields CD8β‐positive TcR γ/δ cells. This is not the result of IL‐7‐induced expression of CD8β on previously CD8β‐negative cells. It is due to IL‐7‐induced expansion of CD8α‐CD8β‐positive TcR γ/δ cells which are shown to be present in the sta

ISSN:0014-2980    

DOI:10.1002/eji.1830220902

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractPhytohemagglutinin (PHA) injection induces transient protease‐sensitive traffic of lymphocytes in skin and other tissues in several species. Examination of the possible roles of cytokines in such reactions showed that recombinant bovine and human tumor necrosis factor (TNF)‐α potently induce dose‐dependent lymphocyte traffic in pig skin (and in other tissues including the draining lymph nodes) with early kinetics and a morphology of the inflammatory reaction similar to that of PHA (peaking 9–12 h). Recombinant human interleukin (IL)‐1α also induces dose‐dependent lymphocyte traffic, but it peaks at 4 h. Entry of labeled lymphocytes into inflammatory sites induced by PHA, TNF‐α and IL‐1α, but not into normal skin, is inhibited by approximately 80 % by their pretreatment with trypsin, indicative of the induction of endothelial determinants recognized by protease‐sensitive surface molecules on the lymphocytes. Even the minimal lymphocyte traffic induced by interferon‐γ and lipopolysaccharide was similarly protease sensitive. At the earliest stage (∼2 h) of significant induction of lymphocyte entry by TNF‐α and IL‐1α the inductive signal for each appears easily saturated. Thus lymphocyte entry is little increased by increasing low cytokine doses over 100‐fold: However, these reactions are additive, and this was used to confirm that they are distinct from each other and from PHA. A further distinction was revealed by the homing of lymphocytes pretreated with pertussis toxin: such lymphocytes were>90 % inhibited in their homing to tissues through constitutive high endothelial venules (HEV) and>60 % inhibited in homing to TNF‐α and IL‐1α skin sites, but unaffected in homing to PHA skin sites (like most non‐HEV‐mediated traffic). Moreover, potent chicken anti‐TNF‐α, which prevented TNF‐induced lymphocyte entry, did not affect PHA‐induced traffic. Thus, these three agents which induce peripheral lymphocyte traffic appear to involve different mechanisms as shown by differences in (i) their kinetics; (ii) the effect of anti‐TNF‐α and (iii) the effect of pertussis toxin treatment of the lymphocytes and by the f

ISSN:0014-2980    

DOI:10.1002/eji.1830220903

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractAntigen challenge has profound effects on a regional lymph node (LN); it leads to an increase in blood flow to the node, and a marked increase in lymphocyte output through the efferent lymphatics. We used the isolated LN model developed in the sheep to see if antigen challenge in a LN resembled inflammation in peripheral tissues. Following stimulation with an antigen (purified protein derivative of tuberculin), lymphocyte output from the LN showed the typical periods of “lymphocyte shutdown” and “recruitment”. The shutdown phase, when cell numbers in efferent lymph dropped by ∼80%, affected almost exclusively the naive‐type (adhesion10, L‐selectin+) T cell population. The large increase in T cell traffic through the node during the recuitment phase was mostly due to CD4+memory‐type T cells and, moreover, the majority of these T cells were L‐selectin−, indicating that these cells were crossing from the blood by a molecular mechanism other than L‐selectin interaction with its ligand, the “lymph node vascular addressin” (MECA‐79). Examination of LN high endothelial venules revealed the presence of vascular cell adhesion molecule‐1 (VCAM‐1), an endothelial adhesion molecule which has been reported to bind preferentially memory‐type T cells in inflammatory lesions. Within the skin, antigen challenge also induced the rapid expression of VCAM‐1 on vascular endothelium. It was purely memory‐type T cells (β1−, L‐selectin+/−) that collected in lymph draining from this tissue. However within chronically inflamed skin, the MECA‐79 determinant appeared on vascular endothelium, and a small proportion of T cells draining from chronically inflamed skin were of naive‐type. The present results illustrate that there are similarities in the cellular and molecular events that characterize antigen stimulation

ISSN:0014-2980    

DOI:10.1002/eji.1830220904

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractCytotoxic T lymphocytes (CTL) are present at high activities in adult patients infected with the human immunodeficiency virus (HIV). In this report, CTL effectors were identified in peripheral blood mononuclear cells (PBMC) of children born to HIV‐1‐infected mothers. These CTL killed HLA‐matched HIV‐1‐infected H9 target cells or doubly transfected P815‐A2‐env, gag or nef mouse tumor cells, which expressed the viral antigens in association with HLA‐A1/A3 or HLA‐A2, respectively. HIV‐1‐specific CTL were detected early after birth (>2 months) and remained present during the asymptomatic phase of the infection. As in HIV‐1‐infected adults, HIV‐specific CTL declined with disease progression. Surprisingly, HIV‐1‐specific CTL were detected in the PBMC of three children who s

ISSN:0014-2980    

DOI:10.1002/eji.1830220905

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractLymphocytes continuously migrate through the body and thus immune competent cells are constantly delivered to most tissues. They interact with high endothelial venules (HEV) via specific homing receptors and vascular addressins, and these molecules seem to be the reason for a preferential homing of B lymphocytes into Peyer's patches and of T lymphocytes into peripheral lymph nodes.When lymphocytes derived from lymph node cell suspensions were applied in thein vitrolymphocyte/endothelium binding assay, the well‐known preference of mouse lymph node B lymphocytes for Peyer's patch HEV compared to peripheral lymph node HEV was confirmed in the rat (2.8 times). When in the samein vitroassay thoracic duct lymphocytes (TDL) were used this preference was far less obvious (1.4 times). However, by injecting rat TDL intravenously and by tracing them directly in HEV, B, T, CD4+and CD8+lymphocytes are seen to enter Peyer's patches and peripheral lymph nodesin vivowithout preference.Thus, in contrast to lymphocytes from lymph node cell suspensions, no evidence was found of a tissue‐specific migration of thoracic duct B, T, CD4+and CD8+lymphocytes at the HEV level. This finding demonstrates the importance of considering both experimental conditions and the cell source used when investigating lymphocyte traf

ISSN:0014-2980    

DOI:10.1002/eji.1830220906

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractRearrangement of DQ52with JHin IgH genes takes place in a large part of lymphocytes at a very early stage of differentiation although usage of DQ52seems to be limited in the functional IgH genes of mature B cells. A possible and likely explanation for this, is secondary D‐JHjoinings occurring after the initial DQ52‐JHjoinings, which becomes possible only when DQ52segments join 5′‐located JHsegments. Previously we reported the non‐random use of JHin joinings with DQ52, in which DQ52‐JH2joinings are dominant. We questioned how the preferential usage of JH2in DQ52‐JHjoinings is determined by utilizing extrachromosomal DNA substrates.Extrachromosomal DNA substrates with a combination of DQ52and multiple JHsegments were prepared. These plasmids with a polyoma‐derived replication system were transfected into pre‐B cell lines and recombination profiles of recovered plasmids were analyzed semi‐quantitatively. Experiments with plasmids containing all four JHsegments in normal configuration showed an apparent high frequency of JH2usage, similar to the rearrangements previously observed in thymocyte genomes. In plasmids containing two JHsegments, when one was JH2, it was rearranged more frequently than the other, independent of its proximity to DQ52. The JH3with recombination signal sequences (RSS) substituted for JH2was rearranged more frequently than the naive JH2itself indicating the importance of RSS. A JH3hybrid with the 200 bp upstream sequence of JH2but excluding RSS, however, failed to increase JH3use. The addition of one nucleotide to the 22‐bp spacer of JH1RSS increased the frequency of JH1usage. These observations suggest that the preferential usage of JH2is determined by the primary DNA sequence and is lar

ISSN:0014-2980    

DOI:10.1002/eji.1830220907

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractThe production of autoantibodies reactive with components of skeletal muscle is characteristic of myasthenia gravis (MG) and is strongly associated with the presence of thymic epithelial tumors in patients with MG. The nucleotide sequences of the heavy and light chain variable regions (VHand VL) of three human monoclonal striated muscle antibodies (StrAb) isolated from thymic B lymphocyte lines from two patients with MG and thymoma were analyzed. The VHand VLgene segments used by these anti‐striated muscle antibodies appear to be derived from the same repertoire of gene segments as have been found in other autoantibodies isolated from patients with a number of different autoimmune diseases. While the IgM StrAb SA‐1A is a direct copy of germ‐line VHand VLgene segments, analysis of the IgG StrAb SA‐4A and SA‐4B, which may be more representative of antibodies found in the serum of MG patients, suggests that the processes of antigenic selection and somatic mutation may contribute to the generation of autoantibod

ISSN:0014-2980    

DOI:10.1002/eji.1830220908

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractIn M54 mice transgenic for a completely rearranged μaheavy chain there is a decrease in total B cells and the rearrangement of endogenous immunoglobulin genes is partially inhibited. Surprisingly, however, endogenous immunoglobulin gene rearrangement and significant heavy chain polypeptide production does occur. We tested the hypothesis that only CD5+B cells produce endogenous immunoglobulin by taking advantage of the fact that X‐linked immune deficient (xid) mice normally are deficient in CD5+B cells. We found that the frequency of CD5+splenic B cells was similar in XxidY transgenic and non‐transgenic F1males, and in XxidX transgenic and non‐transgenic F1females. In both XxidX and XxidY transgenic F1mice some, but not all, splenic B cells are CD11b+. There was a striking deficit of splenic B cells expressing endogenous immunoglobulin in XxidY transgenic mice, although this was not true for peritoneal cells. Thus, the introduction of the 17.2.25 μ transgene does not prevent the development of CD5−B cells nor does it limit endogenous immunoglobulin gene arrangement and expression solely to CD5+B cells. However, in mice capable of expressing B cell surface CD5 or CD11 this transgene can lead to expansion of the fraction of B cells positive for these molecules. We conclude that while the introduction of the 17.2.25 μ transgene alters the frequencies of B cell populations maturation is not limited to one sub

ISSN:0014-2980    

DOI:10.1002/eji.1830220909

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractWe describe two proteins of 24 kDa and 33 kDa (p24 and p33) which associate with H‐2 Kband H‐2 Dbmolecules, respectively, in human cells transfected with H‐2 Kband H‐2 Dbgenes. This association is particularly clear in the mutant cell line T2, in which association of endogenous peptide with newly synthesized class I molecules may not occur (V. Cerundolo et al.,Nature1990.345: 449). We show that p33 is the 33‐kDa form of the human invariant chain which is resident in the endoplasmic reticulum of T2 cells (P. Cresswell,Cold Spring Harbor Symp. Quant. Biol. 1989.LIV: 309). The stability of the invariant chain H‐2 Dbcomplex is critically dependent upon occupation of the class I binding site by peptide ligand. In the absence of peptide, the complex is stable at 4°C whereas following exposure to peptide, the invariant chain dissociates rapidly from H‐2 Dbmolecules (half‐life of 30 min at 4°C). Although the interaction between the human invariant chain and murine H‐2 Dbis unlikely to have any functional significance, the peptide‐induced dissociation of the invariant chain is consistent with a conformational change in H

ISSN:0014-2980    

DOI:10.1002/eji.1830220910

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractMice immunized with attenuatedSalmonella typhimurium, strain SL3235, while protected against virulent challenge, are unable to mountin vivoandin vitroantibody responses to non‐Salmonellaantigens, such as tetanus toxoid and sheep red blood cells, and exhibit profoundly suppressed responses to B and T cell mitogens. Suppression of antibody responses is mediated by macrophage (Mϕ)‐released soluble factors, and is completely reversed by treatment with interleukin (IL)‐4. The present report identifies the suppressor factor as nitric oxide (NO), and provides evidence for a mechanism by which IL‐4 abrogates suppression. Suppressed antibody responses correlated with high levels of NO secretion by splenocytes of SL3235‐immunized mice. NO production was observed only in cultures consisting of the adherent cell fraction of immune splenocytes. Further, immunosuppression was reversed byNG‐monomethyl‐L‐arginine (NMLA), a competitive inhibitor of NO synthesis, and was completely blocked by the addition of excess L‐arginine. Treatment with IL‐4, or anti‐interferon (IFN)‐γ monoclonal antibody (mAb), also abrogated suppression. Optimal reversal of suppression was observed only when NMLA, IL‐4, or anti‐IFN‐γ mAb, was added at day 0 of the 5‐day plaque‐forming cell assay. Treatment with either IL‐4 or anti‐IFN‐γ mAb also lead to a sharp inhibition of NO production by immune spleen cells. Moreover, the addition of IL‐4 to splenic adherent Mϕ inhibited their ability to generate NO. Our data characterize an immunoregulatory pathway, involving IFN‐γ and NO, by which Mϕ mediate immunosuppression and i

ISSN:0014-2980    

DOI:10.1002/eji.1830220911

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY