摘要:

AbstractThe mechanisms responsible for major histocompatibility complex (MHC)‐linked unresponsiveness are still poorly understood. Here we examine the cellular events that follow when B10.A mice are immunized with cow insulin, an antigen to which they make no apparent immunologic response. Despite the fact that there is no detectable antibody or T cell proliferative response to cow insulin, we have been able to clone out responding T cells after priming and restimulatingin vitrowith this “nonimmunogenic” antigen. These cells are L3T4+, and co‐recognize specific antigen and class II MHC gene products. The data demonstrate that “nonresponder” mice to cow insulin have both the capacity to present antigen and T cells capable of recognizing that antigen. The diversity within this population was investigated by analyzing various parameters of cellular activation. These include fine specificity of both antigen and MHC recognition, as well as recognition of allogeneic MHC and Mls determinants. In addition, the antigen‐presenting cell requirements were studied. The results demonstrate that this population comprise a surprisingly heterogeneous group in terms of its repertoire

ISSN:0014-2980    

DOI:10.1002/eji.1830180122

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY

摘要:

AbstractThe correlated expression of several surface antigens (CD 1, class I HLA, CD 3) was examined in human unfractionated thymocytes or selected subsets by using single or double‐color flow cytometry. Prethymocyte subpopulations expressed high levels of HLA. A high proportion of cortical cells expressed low levels of either HLA or CD 3 antigens. Most of these HLA+cortical cells corresponded to the more immature cells and did not express HLA‐B loci products. CD 1 a and CD 3 antigens were expressed in a high percentage of cells and the levels of expression of each antigen in individual cells were inversely correlated. These data and the contour of double‐color histograms are suggestive of the existence of a single pathway of thymocyte differentiation in which class I HLA expression is switched off around the time of the initiation of CD 3 (and Ti?) expression. We suggest that the anti‐major histocompatibility complex (MHC) specificity of the unselected Ti receptor may be incompatible with the expression of MHC products on the cell membrane. At this stage, CD1 antigens, whose expression is inversely correlated with that of HLA, may fulfill the role of MHC antigens. The latter can be re‐expressed later on, once the anti MHC specificities of the Ti receptors have been selected against. Studies onin vitromodulation of HLA molecules by interferon‐a did not reveal any correlation to the expression of CD 1 or CD

ISSN:0014-2980    

DOI:10.1002/eji.1830180123

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY

摘要:

AbstractDuring the parent (P) into F1hybrid graft‐vs.‐host reaction (GVHR), nuclear, leukocyte and erythrocyte autoantibodies are commonly seen. The specificity of these autoantibodies is reminiscent of those found in systemic lupus erythematosus (SLE) patients and SLE‐prone mice. Organ‐specific antibodies, however, including thyroglobulin (Tg) antibodies do not arise spontaneously. There have been conflicting reports about the ability of exogenous Tg to induce an anti‐Tg response during the GVHR. We have re‐examined this question in greater detail.Using the murine P → F1GVHR system, the results of this work demonstrate that mouse thyroglobulin (MTg)‐specific antibodies can be induced during a GVHR. However, mice must both be undergoing a GVHR, and have received exogenous MTg. The highest autoantibody response occurs if mice are injected with mouse thyroid extract or purified MTg at the time of P → F1cell transfer. The anti‐MTg response is MTg dose dependent. The ability to induce anti‐MTg antibody was not major histocompatibility complex restricted, for both the DBA/2→B6D2F1(low responder H‐2 haplotypes to MTg), and AKR or DBA/2→ AKD2FI(high/low responder → high responder haplotype) GVHR gave similar responses. The anti‐MTg titers peaked between days 7–10 and declined thereafter. In contrast, antibodies to dsDNA were not present at this early time, but developed after several weeks. We conclude that organ‐specific autoantibodies can be induced during a GVHR if the appropriate antigen(s) are presen

ISSN:0014-2980    

DOI:10.1002/eji.1830180124

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY

摘要:

AbstractMonoclonal antibodies (mAb) directed against the T cell differentiation antigen CD28 (Tp44) induce proliferation of resting T lymphocytes in the presence of phorbol esters. Moreover, it has been reported that such antibodies augment and sustain T cell proliferation induced by soluble antigens, phytohemagglutinin and anti‐CD3 mAb. Recently, we have shown that in monocyte‐depleted T cell suspensions, anti‐CD28 mAb 9.3 and Kolt‐2 were able to circumvent the requirement for interleukin 2 (IL2) in T cell proliferation induced by soluble anti‐CD3 antibodies. Apart from the synergy of anti‐CD28 antibodies with phorbol myristate acetate and anti‐CD3 antibodies, we found that anti‐CD28 mAb were able to induce T cell mitogenesis in combination with an E rosette‐blocking anti‐CD2 antibody. In this report, we show that antibodies directed against different epitopes on the CD2 antigen can synergize with anti‐CD28 mAb. Furthermore, we demonstrate that proliferation induced through the synergistic action of anti‐CD28 mAb with anti‐CD2 antibodies can be induced in the absence of accessory cells and is accompanied by the production of IL 2 and the excpression of IL2 receptors. We were unable to induce detectable Ca2+mobilization through the simultaneous binding of anti‐CD28 and anti‐CD2 mAb. Taken together, these data show that IL2‐dependent proliferation can be induced through the simultaneous binding of anti‐CD28 and anti‐CD2 antibodies, possibly through phosphatidyl inositol‐independent pathways. The observations may provide further insight into the a

ISSN:0014-2980    

DOI:10.1002/eji.1830180125

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY

摘要:

AbstractTo estimate the extent of the TRGγvariable (V) gene repertoire used in human T cell ontogeny, we have analyzed the variety of Vγ, gene rearrangements in a large series of T and non‐T acute and chronic leukemias. A limited heterogeneity of rearranged fragments was observed: only 13 types of differently rearranged fragments, four of which occurred only once, were found among 80 rearranged chromosomes. Furthermore, in the leukemic population as a whole, the frequency distribution of the most common types of rearranged Vγ, gene‐containing fragments appeared to be nonrandom (p<0.01). Of interest is the clear preference for functionalvs.nonfunctional V, genes (nonfunctional genes being those which carry frameshifts or nonsense mutations but which presumably can still rearrange due to their conserved signal sequences). We discuss the possibilities that this preference may result either from selection of the TRGγproduct at some stage during T cell development or, alternatively, from an intrinsic, antigen‐independent polarity in Vγ, gene

ISSN:0014-2980    

DOI:10.1002/eji.1830180126

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY

摘要:

AbstractAntigen‐specific unresponsiveness lasting at least 2 weeks can be induced in a T cell clone by 24‐h pretreatment with mitogenic anti‐T cell receptor antibodies. In this report the relationship is explored between the antigen‐specific unresponsiveness and activation pathways triggered via the T cell receptor and Thy‐1: the latter pathway is dependent on the former. A mitogenic anti‐Thy‐1 antibody (KT16) made the T cell clone unresponsive to specific antigen and to an anti‐T cell receptor antibody coupled to Sepharose. The unresponsiveness lasted for at least 7 days. However, cells made unresponsive to specific antigen in these ways (the T cell receptor and Thy‐1) could be activated by both interleukin 2 and KT16. KT16 down‐modulated the T cell receptor immediately after the pretreatment, but not on day 7 after the pretreatment. These facts indicate that the state of the unresponsiveness was caused by blocking transduc‐tion of an activation signal triggered by the T cell receptor to an activation pathway shared by the T ce

ISSN:0014-2980    

DOI:10.1002/eji.1830180127

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY

摘要:

AbstractByin situhybridization to frozen sections of mouse embryos, we have localized cells transcribing the Ig Cμ, gene during ontogeny. Transcripts were detected from before day 14 of gestation in individual pre‐B cells in the liver and, surprisingly, in a large proportion of thymocytes between days 15 and 18. The level of μ RNA sequences in the thymus at day 17 was much higher than has been observed for adult thymocytes; from grain counts, the amount of μ RNA was similar to that observed for Ti γ RNA. These findings suggest that Ig and Ti genes are under similar transcriptional controls during Ti gene recombination and that elevated μ RNA production is a normal event early in the intrathymic differentiation of T

ISSN:0014-2980    

DOI:10.1002/eji.1830180128

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY

摘要:

AbstractThe expression of the murine CD 2 gene and the interleukin 2 receptor IL2R has been investigated during fetal thymus ontogeny. CD2 mRNA was undetectable at embryonic day 14 but was readily detectable at day 15 of gestation. Surface IL2R expression was maximal at day 14 and was clearly detectable at day 13. These results indicate that IL2R expression precedes that of CD2 by at least 2 days.

ISSN:0014-2980    

DOI:10.1002/eji.1830180129

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY

ISSN:0014-2980    

DOI:10.1002/eji.1830180130

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY

ISSN:0014-2980    

DOI:10.1002/eji.1830180101

出版商:WILEY‐VCH Verlag GmbH    

年代:1988

数据来源: WILEY