摘要:

AbstractNucleotide sequence analysis of a large number of rearranged immunoglobulin heavy chain V region genes allowed the identification of six new members of the VH7183 gene family. These six new genes plus the eight previously defined genes agrees with the previously estimated complexity of this gene family. Twelve of these genes were represented among the isolated clones. A comparison of the clones, derived from 1‐day‐ and 14‐week‐old BALB/c mice, suggested a biased and developmentally controlled VH7183 gene utilization.Furthermore, a developmentally controlled, non‐random distribution of the functionalvs.non‐functional VHDJHrearrangements was observed among clones utilizing genes of this family, suggesting unsuspected regulatory aspects of Ig rearrangements in the process of B cell differentiation. Finally, a limited junctional diversity was revealed among the neonatal clones as the result of a low frequency of N‐sequence addition. A similar discrepancy was also observed between neonatal and adult VH1558 clones. In conclusion, these data suggest a programmed generation of B cell diversity similar to what has been observed for the establishment of γ/δ T c

ISSN:0014-2980    

DOI:10.1002/eji.1830220112

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractIt has been postulated that thymic nurse cells (TNC), lymphoid‐epithelial complexes composed of thymocytes enclosed within major histocompatibility complex (MHC) class I+and class II+cortical epithelial cells, may provide an optimal microenvironment for the process of T cell selection. By transplanting single TNC in the avian chorionallantoic membrane assay we demonstrate that a significant portion of intra‐TNC lymphocytes (TNC‐L) possess reactivity against self‐MHC molecules. The frequency of these autoreactive cells among TNC‐L exceeds by far that of thymocytes or peripheral blood lymphocytes of the same donor. These results indicate that TNC‐L constitute a T cell population enriched for self‐MHC reactivity,i.e.cells that have undergone positive selection, but not yet deletion and/or

ISSN:0014-2980    

DOI:10.1002/eji.1830220113

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractB cells get help in the antibody response by presenting antigen to helper T (Th) cells. Upon antigen recognition, T cells produce lymphokines that act as growth and differentiation factors for B cells, but resting B cells require additional helper signals that depend on cell contact with an activated Thcell. Like lymphokine secretion, contact help must be induced by antigen recognition or antigen receptor cross‐linking in continuous Thcell lines. In the mouse, most CD4+T cell lines can be classified into one of two stable differentiation states. Th1 or Th2, which produce different lymphokines and have different effector functions, activation requirements and cytoplasmic signalling mechanisms. This report demonstrates additional differences between Th1 and Th2 cell lines in the signalling pathways leading from the T cell antigen receptor to the induction of Thfunctions. In a system dependent on antigen presentation by B cells, B cell proliferation driven by Th2 cells but not Th1 cells was blocked by acute treatment with phorbol esters. Further experiments showed that phorbol esters blocked the induction of both contact help and lymphokine production in Th2 cells but not in Th1 cells. However, depletion of protein kinase C (PKC) activity by prolonged treatment of T cells with high concentrations of phorbol esters blocked induction of contact help and lymphokine production in Th1 cells but not in Th2 cells. These findings support the hypothesis that Th2 cells use a signalling pathway that is independent of PKC and that PKC activation can block this pathway. Since contact help and lymphokine secretion are affected in parallel, this difference between Th1 and Th2 cells probably reflects early events in the signalling pathway. Contact help and lymphokine production could be dissociated with cholera toxin and other cAMP agonists, but this dissociation could be explained by non‐cAMP‐related effects of cholera toxin on induction of contact help in Th2 cells, and by the direct effect of cAMP agonists on interleukin 2 gene transcription in Th1 cells reported by other laborat

ISSN:0014-2980    

DOI:10.1002/eji.1830220114

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractFreshly derived murine CD4+T cells are divided into naive and memory cells based on the expression of CD45 isoforms. Cross‐linking the T cell receptor CD3 complex either by plastic‐bound anti‐CD3 antibodies or the antibody presented on non‐lymphoid Fcγ receptor type II‐positive Chinese hamster ovary cells in absence of competent antigen‐presenting cells fails to activate naive cells to either secrete cytokines or to proliferate. In contrast, memory cells secrete their characteristic cytokines [interleukin (IL) 2, IL4, and interferon‐γ] and show significant proliferation to this stimulus. IL 1 however, is required for their optimal clonal expansion. Differential expression of IL 1 receptor mRNA in memory cells also correlate with their responsiveness to IL 1. Thus, these data reveal a basic difference in the requirements for activation of naive and mem

ISSN:0014-2980    

DOI:10.1002/eji.1830220115

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractWe have cloned circular DNA excised by T cell receptor (TcR)γ1, γ2 and γ3 gene rearrangements in fetal and adult mouse thymocytes. Circular DNA contained a signal joint reciprocal to the genomic V‐J coding joint. Although signal joints without nucleotide insertions are common in immunoglobulin (Ig) and TcR gene rearrangements, the signal joint of γ found in adult thymocytes contained non‐germ‐line element (N) insertions at high frequency, while no insertions were found in fetal thymocytes. Thus developmental stage specificity of TcR γ gene rearrangements is faithfully reflected on the signal joint of excision products. In addition, examination of γ gene excision products revealed circular DNA products of TcR γ‐α transrearrangements, but no evidence for Vγgene replacement in a re

ISSN:0014-2980    

DOI:10.1002/eji.1830220116

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractCD4+T cells recognize antigenic peptides bound to the polymorphic peptide‐binding site of major histocompatibility complex (MHC) class II molecules. The polymorphism of this site is thought to dictate which peptides can be bound and thus presented to the T cell receptor. The mycobacterial 65‐kDa heat‐shock protein (hsp65) peptide 3‐13 is an important T cell epitope: it is immunodominant in the mycobacterium‐specific T cell response of HLA‐DR3+individuals but, interestingly cannot be recognized in the context of any other HLA‐DR molecules. We, therefore, have tested whether the hsp65 epitope p3‐13 is selected for T cell recognition in the context of only HLA‐DR3 molecules by an unique binding specificity for HLA‐DR3. Using biotinylated peptides and EBV‐transformed BLCL comprising all known HLA class II specificities, we find that p3‐13 binds to HLA‐DRw17(DR3) but not to any other HLA‐DR molecule. Conversely, a control peptide p307‐319 influenza hemagglutinin binds to all known HLA‐DR molecules but only weakly to HLA‐DRw17 and HLA‐DR9. Peptide binding could be inhibited by excess unbiotinylated competitor analogue as well as by anti‐DR monoclonal antibodies but not by anti‐class I‐, anti‐DP‐ or anti‐DQ monoclonal antibodies.The amino acid sequence of DRw17 molecules differs uniquely at five positions from the other DRβ1 sequences. Three of these five residues (positions 26, 71 and 74) are potential peptide contacting residues. These residues map closely together in the hypothetical three‐dimensional model of the DR molecule and, thus, most probably form a positively charged pocket, critical for the binding of p3‐13. Interestingly, p3‐13 does not bind to a DR3 variant, the DRw18 molecule. The DRw18β1 chain differs from DRw17 at two major positions, close to or within the DRw17‐specific pocket. These substitutions drastically change the structure and charge of the pock

ISSN:0014-2980    

DOI:10.1002/eji.1830220117

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractA cooperative antibody response in which T helper (Th) cells recognize minor histocompatibility antigens (mha) and B cells recognize Thy‐1 antigen, is used to explore memory in the T cell compartment. In contrast to B cell memory, Thmemory reaches a plateau rapidly, although Thmemory of Thy‐1 itself (or an associated antigen) behaves exceptionally in this respect. The plateau then extends over several weeks at least. Single mha, among them H‐Y, generate detectable memory. Incompatible H‐2 antigens, including class I antigens on their own, inhibit this response through what appears to be a mechanism of intracellular antigenic competition. Antigen presentation in this system is by host cells, as judged by lack of donor‐specific restriction. Memory resides in both the CD45RA+and CD45RA−compartments, although the majority of memory Thcells have the latte

ISSN:0014-2980    

DOI:10.1002/eji.1830220118

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractAn optimized system for probing allo‐immunity to major histocompatibility complex (MHC) antigens by means of adoptive transfer is used to confirm and extend previous work showing that naturally occurring class I MHC antigens, while capable of inducing Thactivity when presented in combination with other allo‐antigens, fail to do so on their own. The Thactivity which they do induce develops slowly, after repeated immunizations, and can properly be described as “latent”. Latency, or “cripticity” as it is also termed, may help explain how autoimmune disease i

ISSN:0014-2980    

DOI:10.1002/eji.1830220119

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractThe α/β T cell receptor (TcR) V gene usage of bronchoalveolar lavage (BAL) lymphocytes and peripheral blood lymphocytes (PBL) from 11 sarcoidosis patients and 4 healthy controls was investigated, using eight α/β TcR V gene product‐specific monoclonal antibodies (mAb). Twenty‐seven percent (3/11) of the sarcoidosis patients had a highly significant increase in Vα2.3+CD4+T lymphocytes in the bronchoalveolar space, while displaying normal frequencies of these T cells in peripheral blood. The reactivities with the remaining seven TcR mAb were normal. In the control group, no compartmentalization of any T cells was seen. Four of the patients expressed the HLA‐DR3 (w17), DQw2 haplotype. Interestingly, the three patients with distinct signs of compartmentalized Vα2.3+CD4+T cells all expressed this HLA haplotype. Additionally, a fourth patient with pronounced, although less significant, accumulation of Vα2.3+CD4+T cells in the lung, was also HLA‐DR3(w17), DQw2+. Expression of Vα2.3+CD4+T cells in BAL of these patients correlated with clinical disease, as revealed on re‐analyzing the four patients after 6 months or longer. Predominant TcR Vα2.3 gene usage in compartmentalized CD4+BAL T lymphocytes, linked to HLA‐DR3(w17), DQw2 haplotype, may thus indicate presence of a specific antigen localized to the lungs of

ISSN:0014-2980    

DOI:10.1002/eji.1830220120

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractThe mucosal immune system of the gastrointestinal (GI) tract consists of Peyer's patches (PP), which are IgA inductive sites, and more diffuse effector regions which include cells in the intraepithelial lymphocyte (IEL) compartment. Since autoimmune MRL lpr/lpr (MRL/lpr) mice develop a proliferating CD3+, CD4−, CD8−(double negative; DN), B220+T cell subset in systemic lymphoid tissue, we have initiated studies to determine the distribution of CD3+, DN, B220+T cells (B220+T cells or lpr/lpr T cells) in the GI immune system. Specifically, we examined T cell subsets separated according to expression of CD4, CD8, Thy‐1, B220, α/β T cell receptor (TcR) and γ/δ TcR in PP and IEL of MRL/lpr mice at 6, 12 and 21 weeks of age. Increased numbers of CD3+T cells were noted in both PP and spleen of 12‐ and 21‐week‐old mice in which the development of autoimmune disorders were also evident. However, normal numbers of CD3+IEL T cells were seen in MRL/lpr mice in all three age groups tested. When the presence of T cell lymphadenopathy was examined in both IgA inductive and effector tissues, the PP followed the B220+T cell pattern seen in the spleen, where ∼ 30%‐50% of CD3+T cells in the PP of 12‐ and 21‐week‐old MRL/lpr mice expressed the phenotype of lpr/lpr T cells and>90% were α/β TcR+. On the other hand, B220+T cells had not developed in PP or spleen of 6‐week‐old MRL/lpr mice. Of interest was the finding that IEL from lpr/lpr homozygous mice did not contain B220+T cells in any age group tested. In this regard, the IEL of MRL/lpr mice comprised an identical pattern and frequency of CD4−/CD8−, CD4+/CD8−, DN and CD4+/CD8+(double positive, DP) T cell subsets as their normal counterparts (i.e.MRL +/+, BALB/c and C3H/HeN mice) which consisted of ∼75%, ∼7.5%, ∼7.5% and ∼10%, respectively. Further, Thy‐1, γ/λ TcR and α/β TcR expression in these four subsets of MRL/lpr IEL were very similar to normal mice. These results suggest that the intestinal IEL compartment is minimally affected by the lpr/lpr mutation which induces T cell abnormalities and indicate that B220+T cells do not preferentially home to IEL. Further, our results support the concept that IEL T cells develop as

ISSN:0014-2980    

DOI:10.1002/eji.1830220121

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY