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PubMed2006

Persistence in Staphylococcus aureus bacteremia: incidence, characteristics of patients and outcome.

Staphylococcus aureus bacteremia often persists. The reasons for persistence and its outcome are poorly defined. We conducted a prospective-observational study among 245 consecutive S. aureus (MRSA: n=125; MSSA: n=120) bacteremias (>or=1 positive blood cultures (BC)) among 234 adults (18-103-y-old; median=59 y) hospitalized during 1 January 2002-31 December 2002 at a 600-bed teaching hospital. Measurements included bacteremia duration, complication-rate (metastatic infection, relapse or attributable mortality) and outcome. Bacteremia duration was measured based on follow-up BC among 193 patients and estimated based on symptoms resolution in the rest. Measured (1-59 d; median=2) and estimated (median=1 d) duration correlated (r=0.885) though positive follow-up BC was often detected without fever (57/105 patients, 54.3%). Persistence (defined as bacteremia for >or=3 d) was noted in 84 cases (38.4%). Complication-rate increased steadily with bacteremia duration (6.6%, 24.0% and 37.7% in bacteremia for 1-2, 3 and >or=4 d, respectively; p=0.05). Cox regression analysis revealed that bacteremia duration correlated positively with endovascular sources (p=0.006), vancomycin treatment (p=0.016), cardiovascular prosthesis (p=0.025), metastatic infections (p=0.025) and diabetes (p=0.038). It is concluded that persistent bacteremia is a feature of S. aureus infection, irrespective of oxacillin susceptibility, associated with worse outcome. Risk factors include endovascular sources, cardiovascular prosthesis, metastatic infections, vancomycin treatment and diabetes. Patients at risk may benefit from novel treatment strategies.

Adolescent↗
PubMed2001

Persistent versus transient map kinase (ERK) activation in the proliferation of lung epithelial type 2 cells.

Type 2 pneumocytes are progenitor cells of alveolor epithelium and important for reepithelialization following lung injury. This study examined the role of persistent versus transient mitogen-activated protein (MAP) kinase (extracellular signal-regulated kinase; ERK) in type 2 cell proliferation. Three different types of agents; epidermal growth factor (EGF), 12-O-tetradecanoylphorbol-13-acetate (TPA), and fetal bovine serum (FBS) induced different patterns of ERK activation. FBS induced a strong and persistent MAP kinase response, whereas the effect of EGF was transient with a strong activation at 5 minutes and only a slight stimulation at 4 hours. The TPA response was more prolonged than the EGF response, but not by far as strong and persistent as the FBS response. Activation by EGF and TPA and the early response induced by FBS were strongly reduced by the MEK inhibitor PD98059. The sustained FBS-induced ERK activation was inhibited by approximately 50%. The total number of cell, the percentage of cells in S and G2/M phase of the cell cycle and the incorporation of 3H-thymidine into DNA were strongly increased in response to FBS, whereas EGF and TPA were without effect. The proliferation was reduced by approximately 50% after pretreatment with PD98059. The results indicate that a persistent ERK activation of a critical size leads to type 2 cell proliferation, and that the proliferative response may also depend on a MEK-independent ERK activation.

Animals↗
PubMed1998

Persistent facial pain following microvascular decompression of the trigeminal nerve.

Pain in the face following microvascular decompression (MVD) can be due to persisting trigeminal neuralgia (TGN) or a variety of other facial pain syndromes. If magnetic resonance tomoangiography (MRTA) indicates continuing vascular compression and the patient has true persistent TGN, then the patient can be relieved of pain by repeating the MVD. When the MRTA is negative for continuing compression alternative techniques may be employed; section of the nerve at the pons may be the treatment of choice for true persistent TGN in the absence of neurovascular compression. In some cases the pain is dysaesthetic in nature and not persistent TGN. This is always associated with previous destructive lesions to the nerve, usually radio-frequency thermocoagulation. When this component to the pain is recognized pre-operatively the patient must be warned not to expect relief of this same component of the pain from MVD. When it is not possible to classify the facial pain clinically, improvement does not occur following MVD even when there is clear evidence of vascular compression on MRTA.

Adult↗
PubMed2000

Electrophysiological indices of persistent post-concussion symptoms.

UNLABELLED: Mild head injuries (MHI) including concussion were once considered transient alterations of function that resulted in no long-term structural or functional effects. This opinion has changed somewhat in recent years, based on the scientific evidence and popular cases in the media that suggest MHI can result in damage that can, in some cases, lead to long-term cognitive sequelae. PURPOSE AND METHODS: An EP/ERP assessment battery is presented as a method for detecting changes in brain function that form the organic basis of persistent post-concussion symptoms (PCS). The primary focus of the paper was directed towards using this battery to determine whether or not brain function in individuals with persistent PCS was different than responses of individuals that comprised a nomative database. RESULTS: Visual and auditory ERPs and visual EPs were beyond a 2.5 standard deviation normal limit in young and older groups of individuals with persistent post-concussion symptoms. CONCLUSIONS: Evidence of changes in brain function in individuals with persistent post-concussion symptoms is consistent with the position that the post-concussion syndrome has a substantial biological, as opposed to a psychological, basis.

Adult↗
PubMed2002

Successful treatment with doxycycline and nicotinamide of two cases of persistent pemphigoid gestationis.

Pemphigoid gestationis (PG) is a rare dermal-epidermal autoimmune bullous disease of pregnancy and postpartum, which relapses more seriously and earlier during following pregnancies. PG also occurs in association with trophoblastic tumours or oral contraceptive treatment. The term 'persistent PG' represents the cases where active disease persists for months to many years after delivery. Four cases of persistent PG have been reported to date in the literature. So far, systemic cortico-steroids have been the main PG therapy and the use of cyclophosphamide, dapsone, pyridoxine, methotrexate, plasmapheresis or ritodrine has also been reported, with contradictory results. In this paper are described two patients with persistent PG who were successfully treated with doxycycline (200 mg/day) and nicotinamide (500 mg/day), a treatment that was demonstrated to be safe and efficacious in bullous pemphigoid.

Adult↗
PubMed1999

Persistent hypertension after removal of adrenal tumours.

OBJECTIVE: To assess the long-term results of operation for adrenal hypertension and to evaluate reasons and potential risk factors for the persistence or recurrence of hypertension. DESIGN: Retrospective clinical study. SETTING: Teaching hospital, Italy. SUBJECTS: 48 patients with benign adrenal tumours who were preoperatively hypertensive and treated by adrenalectomy between 1980 and 1996. MAIN OUTCOME MEASURES: Factors that influenced the persistence of hypertension after removal of the adrenal tumours. RESULTS: During a mean (SD) follow-up of 77 (12) months, 4 (8.3%) patients developed cardiovascular or cerebrovascular complications. 24 patients had had a history of hypertension for less than 5 years and the remaining 24 for 5 years or more. Blood pressure returned to the normal range after operation in 22 patients (46%). 14 patients (29%) had persistent hypertension that required treatment with antihypertensive drugs, but 12 required less intensive treatment than before adrenalectomy. Multivariate analysis showed that age at presentation was the only significant factor predictive of persistent hypertension (p < 0.05); sex, haematochemical tests, raised preoperative blood pressure, duration of hypertension preoperatively, and size of tumour were not. CONCLUSION: The success in reversing hypertension after adrenalectomy for benign tumour is strongly related to age at presentation.

Adolescent↗
PubMed2002

Mutation in loop I of VP1 of Theiler's virus delays viral RNA release into cells and enhances antibody-mediated neutralization: a mechanism for the failure of persistence by the mutant virus.

The DA strain of Theiler's murine encephalomyelitis viruses (TMEV) causes a central nervous system (CNS) demyelinating disease with viral persistence despite the presence of high serum anti-TMEV antibody titers. The DA virus mutant, T81D, was created to have a mutation at position 81 in loop I of VP1, close to the putative virus receptor binding site. T81D showed slower replication in vitro and in vivo. T81D-infected mice developed anti-TMEV antibody responses with no virus persistence. We tested whether the differences between the viruses were due to alteration in virus-cell interactions, or in the resistance to neutralization by anti-TMEV antibody. Using radiolabeled viruses, we found no difference in binding to permissive cell lines between the mutant and wild-type viruses. In a semipermissive cell line, DA virus bound more efficiently than T81D. During the uncoating step, both viruses decapsidated without the production of stable intermediates and 80% of viruses were eluted or decapsidated after 45 minutes. At the final step of uncoating, however, T81D showed a slower rate of RNA release than DA virus into cells using a photoinactivation assay. Anti-TMEV monoclonal and polyclonal antibodies neutralized T81D virus more efficiently than DA virus in suspension. Further, these anti-TMEV antibodies were able to neutralize viruses that had already attached to cells but not internalized (postadsorption neutralization [PAN]). However, DA virus showed significant resistance to PAN after cells were incubated at 37 degrees C compared with T81D-infected cells. The development of resistance to PAN appeared to correlate with the rate of RNA release from virions into cells. In T81D virus infection, the slow RNA release and high susceptibility to neutralization by antibodies would result in a failure to establish virus persistence in vivo. Conversely, rapid RNA release and resistance to neutralization could favor virus persistence in DA virus infection.

Animals↗
PubMed2005

Sporadic amyotrophic lateral sclerosis: a hypothesis of persistent (non-lytic) enteroviral infection.

Because of recently reported reverse transcriptase polymerase chain reaction evidence of enterovirus in sporadic amyotrophic lateral sclerosis (SALS) and because of newly available anti-enteroviral drugs binding enteroviral capsids, it is reasonable to re-formulate an enteroviral hypothesis of SALS using recent advances in molecular virology. Viral persistence is non-lytic and non-cytopathic infection that evades host's immune surveillance. Enteroviruses are known to cause persistent as well as lytic infection both in vitro and in vivo. Both virion as well as host factors modulate between persistent and lytic infection. Apoptosis, or programmed cell death, is a process of active non-necrotic cell death. It has complex interplay with viruses and may be either promoted or opposed by them. Apoptosis is a major factor in motor neuron death in SALS. Viral tropism is the process by which viruses select and propagate to target cells. It is controlled by capsid conformation and surface receptors on host cells. Enteroviruses have a region on their capsids known as the canyon which docks on such receptors. Docking induces conformational changes of the capsid and genome release. Poliovirus, tropic for motor neurons, docks on the poliovirus receptor, about which much is known. The virus penetrates the motor system focally after crossing either the blood-muscle or the blood-brain barriers. It propagates bidirectionally along axons and synapses to contiguous motor neurons, upper as well as lower, which sequester infection and create avenues for spread over long distances. If chronic and persistent rather than acute and lytic, such viruses trafficking in a finite system of non-dividing cells and inducing apoptosis would cause cell death that summates linearly rather than exponentially. Taken together, these explain signature clinical features of SALS - focal onset weakness, contiguous or regional spread of weakness, confinement to upper and lower motor neurons, and linear rates of progression. The hypothesis predicts the following testable investigations: 1) viral detection may be possible by applying amplification technology to optimally acquired nervous tissue processed by laser microdissection; 2) genetic susceptibility factors such as cell surface receptor polymorphisms may combine with sporadic exposure and chance penetration of the motor system in SALS; 3) a transgenic animal model might be created by inserting such genetic factors into an animal host and inoculating intramuscularly rather than intracerebrally biochemical fractions of SALS motor neurons at vulnerable periods in the developmental life cycle of the transgenic host; and 4) continual long-term administration of anti-enteroviral agents called capsid-binding compounds which stabilize capsids and prevent genome release might be efficacious.

Amyotrophic Lateral Sclerosis↗
PubMed2004

Paclitaxel and carboplatin for recurrent or persistent cancer of the cervix.

OBJECTIVE: The objective of this study was to evaluate the effectiveness and degree of toxicity of paclitaxel and carboplatin (PC) combination chemotherapy in patients with recurrent or persistent cervical carcinoma. METHODS: Fifteen patients who received PC chemotherapy for recurrent or persistent carcinoma of the cervix at the Magee-Womens Hospital from 1994-1998 were studied retrospectively. Demographic data, pathology, radiation treatment response, site of recurrence, chemotherapy response, survival rates, and toxicities were reviewed. Months of survival were calculated by the method of Kaplan-Meier from the date after initiation of chemotherapy to death or the last date of follow-up. RESULTS: Fifteen patients received PC for recurrence or persistence of disease with a median of six courses of PC (range, four to 26). Fourteen patients (93.3%) had received prior radiation, and one patient had received surgery as the primary therapy. Four (26.7%) of 15 patients had complete response and five (33.3%) had partial response for an overall clinical response rate of 60%. The median survival of all 15 patients treated with PC was 17 months (range, four to 39). Four patients demonstrated progression of disease while two patients had stable disease. Grade 3 or 4 neutropenia occurred in four patients (26.7%) while one patient (6.7%) suffered from sepsis. Three patients (20%) suffered from Grade 2 anemia and four patients (26.7%) patients developed Grade 2 or Grade 3 neuropathy. There was no incidence of nephrotoxicity. CONCLUSIONS: Paclitaxel/carboplatin chemotherapy appears to have promising activity in recurrent or persistent carcinoma of the cervix with an acceptable toxicity profile. Due to patient convenience and tolerance, consideration should be given to carboplatin as an alternative regimen to cisplatin in combination with paclitaxel.

Adenocarcinoma↗
PubMed2004

The role of budesonide in adults and children with mild-to-moderate persistent asthma.

Asthma, a chronic and potentially life-threatening disease of the airways, affects patients of all ages. Inhaled corticosteroids (ICS) are the recommended first-line therapy for patients with persistent asthma. To review the clinical efficacy and tolerability data available on budesonide in the treatment of mild-to-moderate persistent asthma, a MEDLINE database search was performed for 1996-2003 using the following key words: budesonide, inhaled corticosteroid, efficacy, safety, systemic. When administered once or twice daily, budesonide effectively controls asthma in children, adolescents, and adults with mild-to-moderate asthma. Budesonide can be delivered effectively via a dry powder inhaler (Pulmicort Turbuhaler) in patients aged > or = 6 years or as an inhalation suspension (Pulmicort Respules) in children as young as 12 months. With over 20 years' clinical exposure, budesonide has been demonstrated to be well tolerated in the treatment of chronic asthma in patients as young as 12 months. Specifically, at doses required to treat mild or moderate persistent asthma, budesonide does not affect hypothalamic-pituitary-adrenal axis function, bone mineral density, cataract formation, or final adult height. As Pulmicort Turbuhaler, budesonide is the only ICS to achieve a Food and Drug Administration pregnancy category B rating. Early intervention with budesonide is recommended in asthma management: maximum benefit from therapy is reported in patients treated within 2 years of disease recognition. Budesonide is effective and well tolerated in the control of mild-to-moderate persistent asthma in patients aged 12 months and older. There is no evidence for variation in efficacy in population subgroups.

Administration, Inhalation↗
PubMed2005

Treatment persistence with leukotriene receptor antagonists and inhaled corticosteroids.

BACKGROUND: Leukotriene receptor antagonists (LTRAs) and inhaled corticosteroids (ICSs) must be taken continuously to control persistent asthma. We compared the use of LTRAs and ICSs in patients with similar level of asthma control at treatment initiation with particular attention to treatment persistence. METHODS: Two cohorts of 15 to 45 year old patients with asthma were selected from the Quebec Health Insurance Plan Database between January 1, 1998, and December 31, 2000. We first identified new users of LTRAs and from the remaining patients, we selected new users of ICSs. The ICS patients were then one-to-one matched to LTRA patients on the use of short-acting beta2-agonists and oral corticosteroids in the year prior to the date of the first LTRA or ICS dispensation (index date). We compared compliance to initial therapies using Cox proportional hazards models. RESULTS: Each of the LTRA and ICS cohorts included 2200 patients. Multivariate model showed that compliance was significantly better for LTRAs than for ICSs [adjusted rate ratio of treatment discontinuation (aRR), 0.46; 95% confidence interval (CI), 0.42-0.49]. If in both groups all medications filled were taken at the prescribed dose, the annual percent of days on therapy for LTRA users would have been twice that for ICS users (38% vs. 19%; p<0.0001). CONCLUSION: The findings of this observational study indicate a far from optimal persistence to LTRAs and ICSs in asthmatic patients. The superior persistence to LTRAs might result in better effectiveness.

Administration, Inhalation↗
PubMed2005

Dissipation of chlorothalonil, chlorpyrifos, and profenofos in a Malaysian agricultural soil: a comparison between the field experiment and simulation by the PERSIST model.

A comparison of dissipation of chlorothalonil, chlorpyrifos, and profenofos in a Malaysian agricultural soil between the field experiment and simulation by the PERSIST model was studied. A plot of sweet pea (Pisum sativum) from a farm in the Cameron Highlands was selected for the field experiment. The plot was treated with chlorothalonil, chlorpyrifos, and profenofos. Core soil collection was conducted according to the sampling schedule. Residues of the three pesticides were analyzed in the laboratory. Simulations of the three pesticides' persistency were also conducted using a computer-run software PERSIST. Generally, predicted data obtained using PERSIST were found to be high for the three pesticides except for one field measurement of chlorpyrifos. The predicted data for profenofos, which is the most mobile of the three pesticides tested, was not well matched with the observed data compared to chlorothalonil and chlorpyrifos.

Chlorpyrifos↗
PubMed1958

Studies on persistent infections of tissue cultures. III. Some quantitative aspects of host cell-virus interactions.

Efforts were made to obtain information on some of the quantitative aspects of host cell-virus interactions in MCN cultures persistently infected with Newcastle disease, mumps, and 6-6 viruses, and to elicit the mechanism which permits simultaneous maintenance of virus and cells for indefinite periods of time. It was shown by 4 different technics that only between 10 and less than 1 per cent of the cells yield infectious virus, depending upon the agent employed and, possibly, variations in the conditions of the cultures. No evidence was found to indicate production of non-infectious virus materials. Only the cells carrying infectious virus are capable upon transfer to uninfected cultures to transmit the infection. Cells from persistently infected cultures, which are free of infectious virus at the time of transfer, failed to liberate virus at a later time during incubation periods of up to 4 weeks. The virus-producing cells contain at any given moment not more than 1 infectious unit of virus, suggesting a linear mode of production; i.e., as soon as a virus particle is completed, it is released. Upon inoculation of MCN test tube cultures with chick embryo-adapted NDV persistent infection and interference with vesicular stomatitis virus (VSV) is established with considerable delay. In contrast, following transfer of MCN-adapted NDV, in form of MCN(NDV) cells or first allantoic passage seeds derived therefrom, the number of virus-producing cells increases logarithmically, doubling every 6 to 8 hours until a total of about 10(4) is reached. Thereafter their numbers rise in proportion to the increase in total cell population; i.e., doubling approximately every 48 hours. At the time when 10(4) virus-producing cells are present in the culture interference with VSV is solidly established. In order to obtain this result about 10(6) cells must have adsorbed virus particles, or, in other words, at least 10(6) virus units must have totally been produced instead of the 10(4) measured by infectivity assay. The implications of these and previously reported data have been discussed in detail and a scheme of the course of events in persistently infected cultures has been presented.

Animals↗
PubMed1959

Studies on persistent infections of tissue cultures. IV. Evidence for the production of an interferon in MCN cells by myxoviruses.

In previous reports of this series, it was shown that persistent infection of MCN cultures with certain myxoviruses rendered the cells insusceptible to superinfection by several cytopathogenic viruses. It was thought that production of an interferon might be the cause of this resistance and efforts to confirm this suggestion have been presented. Addition of ultraviolet-inactivated myxoviruses (mumps, Newcastle disease, influenza A, and Sendai) to MCN cultures for periods of 2 to 3 hours, followed by washing and refeeding of the cells, led to the subsequent release into the media of a substance which induced in fresh MCN cells a transitory resistance to infection by vesicular stomatitis virus, and prevented incomplete reproductive cycles of influenza A and Sendai viruses. Media containing this substance were free of detectable hemagglutinating activity and viral complement-fixing antigens. The substance was not neutralized by specific antiviral sera; it was not sedimentable by high speed centrifugation; it was not adsorbed onto red cells; but it was inactivated by trypsin. Thus, its properties matched those of the interferon described by Isaacs and his associates. A comparison of the extent of resistance induced in MCN cells by decreasing doses of ultraviolet-inactivated myxoviruses (interference test) and the protection afforded by the media removed from the cultures prior to challenge and transferred to fresh MCN tubes (interferon test) revealed that wherever interference became detectable in the cells, the media of the corresponding cultures contained some interferon. Interferon was obtained by inactivated myxoviruses also from primary cell cultures by the same techniques, but not from HeLa cells. Interferons derived from one type of culture may protect others equally well or show a certain degree of host specificity in that resistance in homologous cells may be somewhat more pronounced than in heterologous cultures. No resistance could be induced in HeLa cells by the interferon preparations employed. Interferon was detected also in MCN cultures, persistently infected with mumps virus. Its concentration was apparently too small in carrier cultures maintained as routine to be measurable. However, when the cells were grown in heavy sheets in roller bottles, and especially when the volume of medium was reduced for several days prior to harvest, interferon became readily detectable. These results strengthen the suggestion that interferon may play a decisive role in the establishment and maintenance of persistent infections in the system under study. Its nature, source, mode of action, and exact role in persistent infection remains to be elucidated.

Animals↗
PubMed1966

Microbial persistence. I. The capacity of tubercle bacilli to survive sterilization in mouse tissues.

A previously reported form of microbial persistence whereby large populations of tubercle bacilli can be made to "vanish" uniformly from the tissues of mice has been shown to occur generally throughout each group of animals subjected to the experimental procedure; it does not reflect the eradication of the bacilli in the majority of animals with their persistence and ultimate revival in only a minority. The one demonstrable alteration of the tubercle bacilli while "vanished" is that they are sterile. Thus, they are undetectable by cell-free culture, tissue culture, and blind animal passage, i.e. by any method based on microbial multiplication. Whether they have also undergone alteration in morphology and persist in some unconventional form cannot be stated. Acid-fast forms similar to tubercle bacilli can be detected in small numbers by intensified microscopic search of tissue homogenates but the relationship of these forms to the sterile bacilli that ultimately revive is unclear. Thus, the persisting tubercle bacilli are more correctly designated as being in a "sterile state" than one of true latency. The uniform induction of the sterile state is a specific phenomenon requiring the participation of both the nicotinamide derivative, pyrazinamide, and isoniazid. Once assumed, this sterile state is relatively stable and the time required for revival of the tubercle bacilli in the spleens in one-half the animals is seven months. This process can be speeded up by the administration of large doses of cortisone in the third or fourth month after sterilization but revival is not significantly affected by the administration of cortisone earlier.

Animals↗
PubMed1978

Isolation of a heterogeneous population of temperature-sensitive mutants of measles virus from persistently infected human lymphoblastoid cell lines.

Two human lymphoblastoid B-cell lines, WI-L2 and 8866, were infected with the Edmonston strain of measles virus at a multiplicity of infection of 10(-6), and stable persistent infections were established. By immunofluorescence and electron microscopy, the vast majority of cells from both cell lines were expressing viral antigens and releasing virion-like particles. However, very little infectious virus could be detected at 37 degrees C, either by an infectious centers assay or by titration of supernates from persistently infected cultures. When cultures were shifted to 31 degrees C, the cells released a population of virus that was temperature-sensitive. Clonal analysis of supernatant virus at 31 degrees C revealed a highly heterogeneous population of temperature-sensitive mutants, differing in plating efficiency ratios, thermolability, and antigen production at the nonpermissive temperature. Factors such as interferon, defective interfering particles, and extracellular virus do not appear to be important in maintaining the persistent carrier state. These studies have important implications for persistent infections of lymphoid cells in vivo, and the slow neurological diseases associated with measles, subacute sclerosing panencephalitis, and multiple sclerosis.

Antibodies, Viral↗
PubMed1982

Effect of cationized antibodies in performed immune complexes on deposition and persistence in renal glomeruli.

To study the interaction of positively charged antibodies in immune complexes with the fixed negative charge on the glomerular capillary wall, chemical cationization of antibody was accomplished with the maintenance of antigen-binding activity. These cationized antibodies bound rapidly to glomeruli but did not persist. Large-latticed immune complexes formed with these cationic antibodies showed rapid deposition and persistence in renal glomeruli, even when administered in small doses. Electron-dense deposits were present at the anionic sites in the glomerular basement membrane at 1 min and 1 h, with extensive subendothelial deposits present from 12 to 72 h. By 14 d, the deposits were seen in the subepithelial region and the glomerular mesangium. The administration of small-latticed immune complexes prepared with cationized antibody revealed initial deposition without persistence in glomeruli in a manner similar to cationized antibodies alone. Thus, the positive charges on antibodies in immune complexes contribute to the deposition and persistence of the complexes in glomeruli, particularly in the subendothelial area.

Animals↗
PubMed1989

T cell memory. Long-term persistence of virus-specific cytotoxic T cells.

This study documents that virus-specific CTL can persist indefinitely in vivo. This was accomplished by transferring Thy-1.1 T cells into Thy-1.2 recipient mice to specifically identify the donor T cell population and to characterize its antigenic specificity and function by using a virus-specific CTL assay. Thy-1.1+ T cells from mice previously immunized with lymphocytic choriomeningitis virus (LCMV) were transferred into Thy-1.2 mice persistently infected with LCMV. The transferred LCMV-specific CTL (Thy-1.1+ CD8+) eliminate virus from the chronically infected carriers and persist in the recipient mice in small numbers, comprising only a minor fraction of the total T cells. Upon re-exposure to virus, these long-lived "resting" CD8+ T cells proliferate in vivo to become the predominant cell population. These donor CD8+ T cells can be recovered up to a year post-transfer and still retain antigenic specificity and biological function. They kill LCMV infected H-2-matched cells in vitro and can eliminate virus upon transfer into a second infected host. In addition, these long-lived CD8+ T cells appear not to be dependent on help from CD4+ T cells, since depletion of CD4+ T cells has minimal or no effect on their biological properties (proliferation, CTL response, viral clearance). These donor CTL also exhibit an immunodominance over the host-derived LCMV-specific CTL response. When both host and donor T cells are present, the donor CTL response is dominant over the potential CTL response of the cured carrier host. Taken together, these results suggest that virus-specific CTL can persist for the life span of the host as memory cells.

Animals↗