Thymus Pub Date : 1997-01-01

M E Hamel, T J Leupers, A M Kruisbeek

{"title":"Nonresponsiveness and susceptibility to CTLA-4 of antigen-exposed CD4 T cells are not regulated by the Bcl-2 family of apoptotic mediators, but can be restored by IL-2.","authors":"M E Hamel, T J Leupers, A M Kruisbeek","doi":"","DOIUrl":"","url":null,"abstract":"Memory T cells are considered to be less dependent on costimulation and to respond more vigorously to TCR triggering compared to their naive counterparts. We and others, however, observed that memory CD4 T cells display nonresponsiveness to a variety of stimuli, including superantigens and soluble anti-CD3. We now report that CD28-derived costimulation can revert the nonresponsive state of antigen-exposed CD4 T cells. Interestingly, the rescuing effect of CD28 can be completely negated by CTLA-4 engagement. The malfunction of memory T cells is related to increased cell death; the viability can be restored by CD28 engagement and is negatively regulated by CTLA-4 engagement. Importantly, it has been reported that antigen-exposed T cells express lower levels of the anti-apoptotic mediator Bcl-2. In addition, CD28 costimulation was reported to upregulate the expression levels of Bcl-xL. We therefore examined the possible role of Bcl-2 family proteins in the nonresponsiveness of antigen-exposed CD4 T cells, and determined whether CTLA-4, in analogy to CD28, mediates its negative regulatory effects via the Bcl-2 family of apoptotic mediators. Our data indicate that neither the nonresponsiveness nor the susceptibility to CTLA-4 of antigen-experienced CD4 T cells are related to the expression levels of Bcl-2 or Bax. The rescuing effects of CD28, however, may be related to increased Bcl-xL levels. Addition of IL-2 normalizes the nonresponsiveness of memory CD4 T cells and renders these cells resistant to the negative effects of CTLA-4 engagement. Impaired IL-2 production is therefore likely to be the cause of the malfunction and CTLA-4 susceptibility of memory CD4 T cells.","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"24 4","pages":"259-77"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20417514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Loss of T-cell cytotoxic responses in the course of HIV-1 infection. HIV-1感染过程中t细胞毒性反应的丧失。

Thymus Pub Date : 1997-01-01

B Zerhouni, K Sanhadji, J L Touraine

{"title":"Loss of T-cell cytotoxic responses in the course of HIV-1 infection.","authors":"B Zerhouni, K Sanhadji, J L Touraine","doi":"","DOIUrl":"","url":null,"abstract":"T-cell mediated cytotoxicity play an important role in the control of human immunodeficiency virus (HIV) infection. The polyclonal cytotoxic T lymphocyte (CTL) response against target cells infected with a recombinant vaccinia virus expressing Env, Gag, Nef or reverse transcriptase (RT) proteins has been studied in four groups of individuals: acquired immune deficiency syndrome (AIDS) patients, AIDS-related complex (ARC) patients, HIV-1 seropositive subjects and seronegative controls. CTL lines have been generated by non-specific stimulation with phytohemagglutinin and interleukin-2 and target cells have been prepared from autologous B lymphocytes. CTL from asymptomatic and ARC individuals recognized most of the various proteins of HIV-1 but those from AIDS patients had very low or absent responses to the majority of proteins, with the anti-Nef cytotoxic activity decreasing first. Two of 10 AIDS patients had demonstrable recognition of Gag p24, one of RT and eight patients had no recognition of any of the proteins. The effector cells were demonstrated to be predominantly of the CD8+ phenotype, using the appropriate monoclonal antibodies. When heterologous target cells were substituted for autologous cells, the cytotoxic response was abrogated in the vast majority of cases demonstrating its human leucocyte antigen (HLA) class I restriction. Among the 10 HIV-seronegative subjects, nine had no CTL activity against the various HIV-1 proteins but one subject was able to recognize Env and RT. In the evolution of HIV infection from the seropositive stage to AIDS, CTL polyclonal activities progressively decrease, with Nef responses disappearing first, then Env and Gag p55, followed by RT and Gag p24.","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"24 4","pages":"203-19"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20418804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modulation of cytokine gene expression by thymic lympho-stromal cell to cell interaction: effect of retinoic acid. 胸腺淋巴基质细胞与细胞相互作用对细胞因子基因表达的调节:视黄酸的作用。

Thymus Pub Date : 1997-01-01 DOI: 10.1023/A:1016986412325

M. Napolitano, D. Bellavia, M. Maroder, M. Farina, A. Vacca, Luigi Frati, A. Gulino, I. Screpanti

引用次数: 6

Post-thymic T-cell development in the rat. 大鼠胸腺后t细胞发育。

Thymus Pub Date : 1997-01-01

J Kampinga, H Groen, F A Klatter, J M Pater, A S van Petersen, B Roser, P Nieuwenhuis, R Aspinall

引用次数: 0

Presence of nerve growth factor in the thymus of prenatal, postnatal and pregnant rats. 神经生长因子在产前、产后和妊娠大鼠胸腺中的存在。

Thymus Pub Date : 1997-01-01 DOI: 10.1023/A:1016990503061

L. Aloe, A. Micera, L. Bracci-Laudiero, E. Vigneti, P. Turrini

引用次数: 28

Thymic interdigitating cells express thioredoxin (TRX/ADF): an immunohistochemical study of 82 thymus and thymoma samples. 胸腺间指细胞表达硫氧还蛋白(TRX/ADF): 82例胸腺和胸腺瘤样本的免疫组织化学研究。

Thymus Pub Date : 1997-01-01 DOI: 10.11501/3117167

T. Go, N. Isowa, T. Hirata, Junji Yodoi, S. Hitomi, Hiromi Wada

引用次数: 7

The expression of CD4 and CD8 molecules conditions the behavior of V beta + murine thymocytes upon superantigenic challenge. CD4和CD8分子的表达决定了V β +小鼠胸腺细胞在超抗原攻击下的行为。

Thymus Pub Date : 1997-01-01

A Fattorossi, S Baschieri, C Ferlini, G Doria

{"title":"The expression of CD4 and CD8 molecules conditions the behavior of V beta + murine thymocytes upon superantigenic challenge.","authors":"A Fattorossi, S Baschieri, C Ferlini, G Doria","doi":"","DOIUrl":"","url":null,"abstract":"We investigated the capacity of the Staphylococcal enterotoxin (SE) B, a superantigen (SAg) specific for TCR V beta domain, to modulate V beta 8+ thymocytes selection in adult mice. Thymocytes were collected at various time intervals after SEB injection (10 and 100 micrograms) and V beta 8+ modulation was analysed by three color flow cytometry. SEB failed to affect V beta 8+ thymocytes comprised in the less mature compartments, namely, CD4+8+ and CD4-CD8-, whereas it selectively affected V beta 8+CD4+8+ (downward modulation) and V beta 8+CD4-8+ thymocytes (upward modulation). The different response to SEB challenge between CD4+8- and CD4-8+ thymocytes appeared dependent on the CD4/MHC class II interaction, as V beta 8+CD4-8+ thymocytes carrying a transgenic CD4 molecule capable of interacting with MHC class II showed the same response of V beta 8+CD4+8- thymocytes. At variance with thymocytes, however, V beta 8+CD4+8- and V beta 8+CD4-8+ splenic T lymphocytes responded to SAg challenge in identical manner (upward modulation) highlighting the importance of maturation status and/or microenvironment in SAg response. V beta 8+ thymocytes remaining in the thymus were assessed for their capacity to respond to a SAg challenge. Thus, thymocytes were obtained at various time intervals after SEB injection and cultured in the presence of SEB or SEA, a Sag specific for V beta 10 as control. A reduced mitotic response to SEB but not to SEA was noticed irrespective of the number of V beta 8+ responding cells present in culture. It is concluded that SAgs affect TCR specific thymocytes by conditioning their redistribution and inducing an anergic status.","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"24 3","pages":"133-45"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20099010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Presence of nerve growth factor in the thymus of prenatal, postnatal and pregnant rats. 神经生长因子在产前、产后和妊娠大鼠胸腺中的存在。

Thymus Pub Date : 1997-01-01

L Aloe, A Micera, L Bracci-Laudiero, E Vigneti, P Turrini

引用次数: 0

Detection of Fas and its ligand, FasL, in mouse thymus by in situ hybridization. 小鼠胸腺Fas及其配体FasL的原位杂交检测。

Thymus Pub Date : 1997-01-01

M Gienau, K U Hartmann

引用次数: 0

Interleukin (IL)-2 deficiency aggravates the defect of natural killer cell activity in AIDS patients. 白细胞介素(IL)-2缺乏加重了艾滋病患者自然杀伤细胞活性的缺陷。

Thymus Pub Date : 1997-01-01

B Zerhouni, K Sanhadji, L Kehrli, J M Livrozet, J L Touraine

{"title":"Interleukin (IL)-2 deficiency aggravates the defect of natural killer cell activity in AIDS patients.","authors":"B Zerhouni, K Sanhadji, L Kehrli, J M Livrozet, J L Touraine","doi":"","DOIUrl":"","url":null,"abstract":"A decrease in natural killer (NK) cell activity is a common feature of the immune dysfunction found in patients with human immunodeficiency virus (HIV)-induced acquired immune deficiency syndrome (AIDS). The present study was aimed at exploring the NK and the lymphokine-activated killer (LAK) cell activities of lymphocytes from HIV-seropositive subjects. The in vitro production of interleukins (IL-2 and IL-10) in response to mitogens was also studied. Two groups of HIV-seropositive subjects were studied: asymptomatic and AIDS patients. Controls were normal blood donors. The NK cell activity in peripheral blood mononuclear cells (PBMC) from AIDS patients was significantly lower than that in PBMC from both HIV-seronegative subjects and asymptomatic patients. There was no significant difference between asymptomatic patients and controls. Exposure of PBMC from all three groups of individuals to an optimal dose of IL-2 in vitro enhanced LAK cell activity. At all three effector: target cell ratios, the LAK activity in AIDS patients remained below that in normal subjects. However, the proportional increase of lytic activity with IL-2 was slightly higher in AIDS patients than in HIV-seronegative subjects. The mitogen-induced production of IL-2 was especially reduced in AIDS patients. In contrast, very high levels of mitogen-induced production of IL-10 were found in the AIDS group, as compared to asymptomatic subjects or to controls. We therefore conclude that the alteration of NK cell activity occurs at an advanced stage of HIV infection, that the reduction of cytotoxic activity is partially restored by exogenous IL-2, and that decreased production of IL-2 and increased production of IL-10 may account for part of this reduction in cytotoxicity.","PeriodicalId":76738,"journal":{"name":"Thymus","volume":"24 3","pages":"147-56"},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20099011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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