Apoptotic depletion of CD4+ T cells in idiopathic CD4+ T lymphocytopenia.

Laurence, Jeffrey; Mitra, Debashis; Steiner, Melissa G.; Lynch, David H.; Siegal, Frederick P.; Staiano‐Coico, Lisa

doi:10.1172/jci118464

Cited by 103 publications

(71 citation statements)

References 51 publications

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“…The requirement for T-cell activation seems to be a common feature of monocyte-dependent apoptosis mediated by Fas-FasL interaction (30,34,35). Laurence et al suggested that patients with ICL linked to clinical immune suppression have evidence for accelerated T cell apoptosis in vitro (22) and Roger et al reported an ICL case in which CD4 positive T lymphopenia was correlated with an overexpression of CD95 (Fas receptor) together with spontaneous and Fas-induced apoptosis (24). The result of the present patient was compatible with previous reports.…”

Section: Discussionmentioning

confidence: 99%

Pleural Cryptococcosis with Idiopathic CD4 Positive T-lymphocytopenia

et al. 2004

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A 19-year-old man was admitted to our hospital because of chest pain. He was diagnosed as having pleural cryptococcosis by pleural biopsy. His CD4 positive Tlymphocyte count was low (<300 µl) and there was no evidence of human immunodeficiency virus infection. He was successfully treated with fluconazole. However, his CD4 positive lymphocyte counts remained low after the recovery and he was diagnosed as idiopathic CD4 positive T-lymphocytopenia. Pleural cryptococcosis is rare and its predisposing condition is still controversial. To our knowledge, this is the first case of pleural cryptococcosis associated with idiopathic CD4 positive T lymphocytopenia. (Internal Medicine 43: 977-981, 2004)

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Section: Discussionmentioning

confidence: 99%

Pleural Cryptococcosis with Idiopathic CD4 Positive T-lymphocytopenia

et al. 2004

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“…P-values (log-rank test) corresponding to the differences between the growth curves of CPT-11 treated HT29 and HT29A3 tumours, are indicated Mice were treated with CPT-11 at low dose (A) (10 mg kg -1 at 4-day intervals × 4) or high dose (B) (40 mg kg -1 at 4-day intervals × 6). P-values (log-rank test) corresponding to the differences between the growth curves of CPT-11 treated LoVo and X17LoVo tumours, are indicated 270-290 of the fas-apo-1 receptor gene coding sequence (Laurence et al, 1996)) fasR-2: AS 5′-CCT TGG TTT TCC TTT CTG TGC-3′ (bases 797-817 of the fas-apo-1 receptor gene coding sequence (Laurence et al, 1996)) hprt-1: S 5′-CAA CAG GGG ACA TAA AAG TAA T-3′ (bases 414-435 of the hprt-gene coding sequence) hprt-2: AS 5′-AGT CCG TCA TAT TAG GTT TCT-3′ (bases 534-554 of the hprt-gene coding sequence).…”

Section: Pcr Primersmentioning

confidence: 99%

Sensitivity to CPT-11 of xenografted human colorectal cancers as a function of microsatellite instability and p53 status

Bras-Gonçalves

Rosty²,

Laurent‐Puig³

et al. 2000

Br J Cancer

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Summary Biological parameters influencing the response of human colorectal cancers (CRCs) to CPT-11, a topoisomerase 1 (top1) inhibitor, were investigated using a panel of nine CRCs xenografted into nude mice. CRC xenografts differed in their p53 status (wt or mut) and in their microsatellite instability phenotype (MSI + when altered). Five CRC xenografts were established from clinical samples. All five had a functional p53, two were MSI + and three were MSI -. Tumour-bearing nude mice were treated intraperitonealy (i.p.) with CPT-11. At 10 mg kg -1 of CPT-11, four injections at 4-day intervals, four of the five xenografts responded to CPT-11 (growth delay of up to 10 days); the non-responder tumour was MSI -. At 40 mg kg -1 of CPT-11, six injections at 4-day intervals, the five CRCs displayed variable but marked responses with complete regressions. In order to assess the role of p53 status in CPT-11 response, four CRC lines were used. HT29 cell line was MSI -/Ala273-mutp53, its subclone HT29A3 being transfected by wtp53. LoVo cell line was MSI + /wtp53, its subclone X17LoVo dominantly expressed Ala273-mutp53 after transfection. LoVo tumours (MSI + /mutp53) were more sensitive than X17LoVo (MSI + /mutp53. HT 29 tumours (MSI -Imutp53), were refractory to CPT-11 while HT29A3 tumours (MSI -/wtp53) were sensitive, showing that wtp53 improves the drugresponse in these MSI -tumours. Levels of mRNA expression of top1, fasR, TP53 and mdr1 were semi-quantified by reverse transcription polymerase chain reaction. None of these parameters correlated with CPT-11 response. Taken together, these observations indicate that MSI and p53 alterations could be associated with different CPT-11 sensitivities; MSI phenotype moderately influences the CPT-11 sensitivity, MSI + being more sensitive than MSI -CRC freshly obtained from patients, mutp53 status being associated with a poor response to CPT-11. © 2000 Cancer Research Campaign Keywords: CPT-11; MSI; p53; top1; human colorectal cancer; nude mice (2000) 82(4), 913-923 © 2000 Cancer Research Campaign DOI: 10.1054/ bjoc.1999.1019, available online at http://www.idealibrary.com on et al, 1998). Cells with functional wtp53 are found to be dramatically more sensitive to many of the commonly used anticancer agents (Fujiwara et al, 1994;Lowe et al, 1993Lowe et al, , 1994McDonald and Brown 1998). In MSI + tumours, defects in mismatch repair genes could lead to the accumulation of unrepaired or misrepaired DNA during DNA replication, rendering them more sensitive for CPT-11 effect.Other resistance mechanisms to CPT-11 could also be implicated. Overexpression of the multidrug resistance gene product, P-glycoprotein, encoded by the mdr1 gene has been incriminated in tumour cell resistance to numerous compounds (Gottesman et al, 1996). Its role in the lack of sensitivity of tumour cells to CPT-11 has been described . Two groups have recently shown that colorectal cancers of the colonic mucosa express the fas receptor (fasR), a cell membrane determinant which triggers the apoptotic casc...

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“…[13][14][15][16] In the latter scenario, lymphopenia resulting from up-regulated in vivo apoptosis is the clinical finding in human immunodeficiencies, such as idiopathic CD4 ϩ T lymphocytopenia, and it correlates with increased levels of CD95 and CD95L, a finding also observed in patients with CD8 ϩ T lymphopenia. 17 Lymphocytopenias found in adults could also result from adenosine deaminase deficiency. 18 Other factors implicated in different forms of apoptosis are reactive oxygen species (ROS).…”

Section: Introductionmentioning

confidence: 99%

Red blood cells inhibit activation-induced cell death and oxidative stress in human peripheral blood T lymphocytes

Fonseca

Porto

Uchida

et al. 2001

Blood

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IntroductionProgrammed cell death, or apoptosis, is a physiological process that contributes to the homeostasis of multicellular organisms. Apoptosis resulting from activation of T cells-ie, activationinduced cell death (AICD)-is thought to serve as a feedback mechanism that deletes activated T cells. 1 Contrary to immature thymocytes and transformed T-cell lines, resting T cells are highly resistant to apoptosis after initial activation but then become highly susceptible. [2][3][4] Accordingly, most studies on AICD have focused on the study of interactions between the death receptors, CD95 (Fas) and tumor necrosis factor (TNF)-␣ receptor, with their agonists, CD95L (Fas ligand) and TNF-␣, on activated T cells and T-cell hybridomas 5,6 (for review, see 7 ). Quiescent normal T cells express low or nondetectable levels of CD95 and CD95L, but mitogenic activation of primary T cells markedly increases their expression. 8,9 Other members of the TNF-␣ receptor family, such as TRAIL-R1 and TRAIL-R2, can also trigger apoptosis in susceptible cells after binding of their ligands. 7 Despite the important role played by the death receptors, growing evidence indicates that environmental constituents, such as nonlymphoid secreted factors and cytokines, can modulate apoptosis of activated T cells, thus emphasizing the significance of the environment in the maintenance of T-cell homeostasis. [10][11][12] Any imbalance in the apoptotic process may result in either of 2 possible scenarios: lymphocyte accumulation or lymphocyte depletion. In the former, lymphoproliferative disorders-now designated as autoimmune lymphoproliferative syndrome-result from downregulated in vivo apoptosis, develop in mice and in humans, result from genetic mutations in CD95 or its ligand, and are associated with autoimmune phenomena. [13][14][15][16] In the latter scenario, lymphopenia resulting from up-regulated in vivo apoptosis is the clinical finding in human immunodeficiencies, such as idiopathic CD4 ϩ T lymphocytopenia, and it correlates with increased levels of CD95 and CD95L, a finding also observed in patients with CD8 ϩ T lymphopenia. 17 Lymphocytopenias found in adults could also result from adenosine deaminase deficiency. 18 Other factors implicated in different forms of apoptosis are reactive oxygen species (ROS). Several studies have provided evidence for the involvement of ROS in apoptosis of T-cell blasts and hybridomas by using antioxidants such as N-acetyl cysteine and glutathione. 19,20 Apoptosis in these cells is the consequence of changes in mitochondrial permeability and the subsequent release of ROS. 21 Studies performed with primary T cells, however, indicate that the formation of intracellular ROS is necessary for T-cell activation and IL-2 secretion but also regulates activationinduced T-cell apoptosis, therefore suggesting that intracellular ROS could play a role in peripheral T-cell homeostasis. [22][23][24] Nevertheless, studies with primary T cells are usually performed in cultures lacking other "nonlymphoid" cells, albeit...

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Apoptotic depletion of CD4+ T cells in idiopathic CD4+ T lymphocytopenia.

Cited by 103 publications

References 51 publications

Pleural Cryptococcosis with Idiopathic CD4 Positive T-lymphocytopenia

Pleural Cryptococcosis with Idiopathic CD4 Positive T-lymphocytopenia

Sensitivity to CPT-11 of xenografted human colorectal cancers as a function of microsatellite instability and p53 status

Red blood cells inhibit activation-induced cell death and oxidative stress in human peripheral blood T lymphocytes

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