Chaperonins of the purple nonsulfur bacterium Rhodobacter sphaeroides.
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Adenosine Triphosphatases↗
Biomedical subjects
W T Lee
Publications and source records attributed to W T Lee.
A capsaicin-receptor antagonist, capsazepine, reduces inflammation-induced hyperalgesic responses in the rat: evidence for an endogenous capsaicin-like substance.
In the present study, the presence of an endogenous capsaicin-like substance and the role of capsaicin receptors in nociception during inflammation were assessed using Fos immunohistochemistry and the paw-withdrawal test in rats. Intradermal injection of carrageenan in the hind-paw produced inflammation in the foot pad, increased the number of cells exhibiting Fos-like immunoreactivity in the dorsal horn of the spinal cord, and decreased the paw-withdrawal latency. Intradermal injection of capsazepine, a capsaicin-receptor antagonist, significantly reduced the number of cells exhibiting Fos-like immunoreactivity, significantly increased the paw-withdrawal latency, but did not decrease inflammation induced by carrageenan injection. Intradermal injection of capsaicin or formalin also increased Fos-positive neurons. Capsaicin- or formalin-induced Fos expression was reduced in both cases by pretreatment of capsazepine, but to a much lesser extent for formalin. The capsazepine inhibition of carrageenan inflammation-induced hyperalgesic responses strongly suggests that an endogenous capsaicin-like substance is released in inflamed tissues and produces nociceptive neural impulses by acting on capsaicin receptors present on sensory neurons. Furthermore, our results indicate that capsaicin receptors take part only in generating nociceptive signals in sensory neurons, but not in activating the inflammation-promoting cells.
Animals↗
The controversy regarding diagnostic criteria for early myoclonic encephalopathy.
To re-evaluate the diagnostic criteria for early myoclonic encephalopathy (EME), the following study was done. During the past 2 years, five patients with erratic, fragmentary myoclonus of neonatal onset, in association with other types of seizures, were analyzed with regard to etiologies, electroclinical features and their evolution, using a series of examinations including electroencephalographies (EEGs) and metabolic investigations. Of these five patients, three were diagnosed to have non-ketotic hyperglycinemia (NKH); one was pyridoxine-dependent; the other was cryptogenic. Only two cases (one NKH and one cryptogenic) had initial typical suppression-burst (S-B) EEG pattern, which subsequently evolved into multiple paroxysmal abnormalities with random asynchronous attenuation (MP-AA) pattern. The other two cases with NKH had MP-AA EEG pattern throughout both awake and sleep recordings in two consecutive EEG studies. All three cases with NKH survived with increasing microcephaly, muscle tonicity; all developed infantile spasm with hypsarrhythmia on EEGs. The patient with pyridoxine-dependency had an initial MP-AA EEG pattern, which converted into S-B pattern after the first use of pyridoxine, eventually becoming normal after a supplement with the second-dose of pyridoxine. In conclusion, either S-B or MP-AA pattern may reflect the severity of the underlying pathologies or the disease stages. These results suggest that, from both etiological and electroclinical viewpoints, EME may represent a broader spectrum than previously recognized. The still ongoing controversy regarding whether the S-B pattern should be recognized as the sole EEG criteria for the diagnosis of EME needs further experience to clarify.
Age of Onset↗
Determinants of axial and peripheral bone mass in Chinese adolescents.
OBJECTIVE: To determine the relation of puberty, physical activity, physical fitness, and calcium intake with bone mineral content (BMC) of the distal radius, and on bone mineral density (BMD) of the L2 to L4 vertebrae in a group of healthy Chinese adolescents. DESIGN: Cross sectional survey. SUBJECTS: A group of 179 healthy Chinese adolescents (92 boys and 87 girls) aged 12 to 13 years enrolled in the first year of the Tii Junior High School in Shatin, Hong Kong. Ninety four of the pupils enrolled were in the physical education major class (PE), and the other 85 were in the art major class (ARTS). MAIN OUTCOME MEASURES: Correlation of BMC of the distal radius and BMD of the L2 to L4 vertebrae with level of physical activity, physical fitness (isometric and isokinetic), muscle strength of the upper and lower limb, and calcium intake. RESULTS: BMC of the distal radius and BMD of the L2 to L4 vertebrae were significantly positively correlated. Univariate and regression analysis showed that age, pubertal staging, physical fitness, and muscle strength were significantly associated with bone mass in a positive way. Calcium intake and type of sport practised did not exert a significant influence on BMC of the distal radius and BMD of the L2 to L4 vertebrae in boys. The results for the BMD of the L2 to L4 vertebrae were similar in girls and boys; however, in girls, the BMC of the distal radius had a negative correlation with calcium intake. Physical fitness was a significant positive predictor of BMD of the L2 to L4 vertebrae. CONCLUSIONS: Among Chinese adolescents bone mass was positively influenced by certain measures of physical fitness as well as by age, weight, and pubertal stage.
Adolescent↗
Risk factors for development of acute renal failure (ARF) requiring dialysis in patients undergoing cardiac surgery.
Acute renal failure (ARF) is one of the major complications after cardiopulmonary bypass for open heart operations. The present study was undertaken to identify the risk factors for the development of ARF following cardiopulmonary bypass (CPB). Four hundred and forty-seven consecutive patients who underwent open heart procedures from July 1994 to June 1995 were analyzed retrospectively. Their mean age was 55.6 +/- 14.2 (SD) years (range, 18 to 80). Dialysis was instituted whenever a patient exhibited inadequate urine output (<0.5 mL/kg/hr) for 2 to 3 hours despite correction of hemodynamic status and diuretic therapy, especially if fluid overload, hyperkalemia, or metabolic acidosis were also present. Twenty variables were analyzed by univariate analysis; these included nine preoperative variables--age, sex, hypertension, atherosclerosis, diabetes mellitus, left ventricular end-diastolic dimension (LVEDD) >5 cm, preoperative congestive heart failure, renal insufficiency (serum creatinine > or =130 micromol/L on two occasions), and sepsis--10 intraoperative variables--duration of CPB, redo procedures, emergency surgery, use of intraaortic balloon pump (IABP) in operating room, use of gentamicin, use of ceftriaxone, use of sulbactam/ampicillin, requirement of deep hypothermic circulatory arrest, duration of low mean perfusion pressure (mean pressure <50 mmHg for more than 30 minutes), operation on multiple valves--and one postoperative variable--significant hypotension (systolic blood pressure less than 90 mmHg for more than 1 hour). Significant variables or the variables having a trend (p<0.1) to be associated with ARF were included in stepwise multiple logistic regression analyses. Three regression analyses were performed separately. The incidence of ARF requiring dialysis in the study period was 15.0%. Significant risk factors for whole group of patients (regression I) were preoperative renal insufficiency (p<0.0001), postoperative hypotension (p<0.0001), cardiopulmonary bypass time more than 140 min (p<0.005), preoperative congestive heart failure (p<0.01), and history of diabetes mellitus (p<0.01). The risk factors in the valve group of patients (regression II) were preoperative renal insufficiency (p<0.0001) and postoperative hypotension (p<0.05). Risk factors in the CABG patients (regression III) were postoperative hypotension (p=0.0001), CPB time more than 140 min (p<0.05), preoperative renal insufficiency (p<0.05), and age (p<0.05). The authors conclude that preoperative renal insufficiency and postoperative hypotension are the most important independent risk factors for ARF in postcardiac surgical patients. In addition, CPB time greater than 140 minutes and old age are also independent risk factors for ARF in CABG patients. CPB time more than 140 minutes, history of diabetes mellitus, and preoperative congestive heart failure are independent risk factors for development of ARF in our total group of patients. These findings may have important clinical implications in the prevention of ARF in postcardiac surgical patients.
Acute Kidney Injury↗
Immunoreactivity of androgen receptor protein in sexually dimorphic spinal motonucleus in neonatal male rats.
The spinal motonucleus of the genitofemoral nerve regulating scrotal temperature can also be related to prenatal and neonatal testicular descent by gubernacular change in rats, and a sexually dimorphic-like bulbocavernosus/dorsolateral motonucleus. There is a hypothesis that neonatal androgen affects these motonuclei, and induces development of sexual organs through neural stimulation. Until now, the accumulation of isotope-labelled androgen and the immuno-reactivity of androgen receptor protein in each sexually-dimorphic spinal motonucleus have been revealed in adult rats but they have not been established in rats during neonatal periods. To investigate the presence of the androgen receptor in spinal sexually-dimorphic motonuclei in the neonatal period, we evaluated the androgen receptor immunoreactivity of these motonuclei. In Sprague-Dawley male rats, the lumbar spinal cords were resected at postnatal days 3, 10 and 30, and stained immunohistochemically using polyclonal antibody of androgen receptor protein. The immunoreactivity of androgen receptor protein was observed in the cells of the genitofemoral motonucleus from the 13th thoracic to the 2nd lumbar spinal cord and the bulbocavernosus/dorsolateral motonucleus was observed from the 4th to 5th lumbar spinal cord in all age groups. The proportional areas of both motonuclei at days 3 and 10 on cross-section were larger than at day 30. The motonuclei at days 3 and 10 were similar in all age groups. With the above results, the presence of androgen receptor protein was confirmed in the genitofemoral and bulbocavernosus/dorsolateral motonucleus from neonate to day 30. The larger proportional area of these motonuclei in neonates may indicate an active role for these motonuclei during the neonatal period. Although the immunoreactivity does not directly imply the presence of a functional receptor, neonatal androgen could be responsible for the development of sexual organs through the spinal motonucleus.
Animals↗
A non-fatal impalement injury of the thorax.
Impalement is an uncommon injury with only occasional reports in the literature. There are even fewer reports of impalement injuries limited to the thorax. We report herein the case of a 24-year-old man who survived impalement injury of the left side of the thorax with a steel rod while working at a construction site. The great vessels of the thorax were spared but the second thoracic vertebra was fractured resulting in complete paralysis of the left lower limb. The precise nature and extent of the injury were determined pre-operatively by computed tomography and aortography. The important principles of surgical management contributing to the successful outcome are described, these being minimal manipulation of the impalement object before and during transport, careful pre-operative planning and a multidisciplinary approach.
Accidents, Occupational↗
In vivo the environmental pollutants lead and mercury induce oligoclonal T cell responses skewed toward type-2 reactivities.
An oligoclonal utilization of Vbetas has been reported for pathogenesis of several autoimmune diseases, anti-tumorigenic activity, and superantigen-regulation of thymic T cell development. Altered ratios of Th1 and Th2 cells also are observed in immunodysregulations, leading to impaired cell-mediated immunity with an increased incidence of infectious disease or cancer and/or aberrant immunity that could culminate with an autoimmune disease. Lead (Pb) and mercury (Hg) are known pollutants with immunodisrupting activities; Hg is known to cause autoimmune glomerulonephritis. Both metals are known to suppress host resistance to pathogens. To further evaluate the manner by which these metals cause in vivo immunomodulation, their in vivo effects on Vbeta expression were evaluated along with the Th1 and Th2 frequency. Exposure of BALB/c mice to PbCl2 or HgCl2 induced an oligoclonal response with increases of Vbeta 5+, Vbeta 7+, and Vbeta 13+ CD4+ splenic, but not thymic, T cells. A significantly skewed frequency of Pb-induced splenic Th2 cells expressing Vbeta 7 or Vbeta 13 over Th1 cells was determined by limiting dilution analysis, but this Th2 predominance was not observed with CD4+ T cells expressing Vbeta 8. DO11.10 transgenic mouse exposed to Pb and antigen also demonstrated a skewed type-2 response evidenced by significantly increased IgE levels, lowered IFN-gamma levels, and increased IgG1 and lowered IgG2a anti-OVA levels. Even in the absence of specific T cell responses to a Pb-induced antigen, due to the restricted T cell specificity in the transgenic mouse model, Pb still was able to skew the response toward type-2 reactivity. However, this skewing occurred only in the presence of antigen. Therefore, the Pb-induced oligoclonal T cell response in BALB/c mice which must be initiated by self-antigens and was predominately type-2 may be responsible for autoantibody production and the detrimental health effects associated with Pb exposure.
Animals↗
Memory T cell tolerance to superantigens is not due to increased susceptibility to apoptosis.
Naive (virgin) and memory T lymphocytes differ markedly in their response to superantigens (SAg). When cultured with the SAg staphylococcal enterotoxin B (SEB), virgin but not memory CD4(+) T cells proliferate and secrete lymphokines. Memory cells do express increased levels of activation markers after interaction with SEB, which suggests that the cells are not ignorant of the SAg. In this report, we have considered whether SEB, rather than activating memory cells, promotes their death by apoptosis. Our results indicate that while in vivo exposure to SEB induces apoptosis, there is no greater level of cell death in the memory cell population relative to virgin cells. Further, elimination of the Fas-mediated cell death pathway does not permit memory cells to be stimulated by SEB. Memory T cells from either Fas-expressing or Fas-deficient (MRL-lpr/lpr) mice are hyporesponsive to SEB. Blockade of Fas/Fas-ligand interactions by a Fas-Fc chimeric protein does not permit BALB/c memory cells to proliferate upon culture with SEB. These results provide evidence that the failure of memory T cells to respond to SEB is not due to cell death and that inactivation (anergy) is the likely fate of these cells when they encounter SEB.
Animals↗
Duplication of proteolipid protein gene: a possible major cause of Pelizaeus-Merzbacher disease.
The classic form of Pelizaeus-Merzbacher disease is a rare X-linked dysmyelinating disorder of the central nervous system in which mutations of the proteolipid protein gene have been reported since 1989. However, mutations in the proteolipid protein gene have been identified in only 10 to 25% of all cases of Pelizaeus-Merzbacher disease, which suggests that other genetic aberrations may be present. Recently, proteolipid protein gene overdosage was discovered to cause Pelizaeus-Merzbacher disease. By using comparative multiplex polymerase chain reaction and restriction fragment length polymorphism analysis, we confirmed the proteolipid protein gene duplication as the cause of Pelizaeus-Merzbacher disease in 4 patients from 3 Chinese families with Pelizaeus-Merzbacher disease with no detectable exonic mutations. These results support the hypothesis that proteolipid protein gene duplication may be a major cause of Pelizaeus-Merzbacher disease in all ethnic groups and also suggest that the molecular diagnosis of Pelizaeus-Merzbacher disease should therefore include duplication analysis of proteolipid protein gene.
Diffuse Cerebral Sclerosis of Schilder↗
Bone mineral acquisition in low calcium intake children following the withdrawal of calcium supplement.
Our recent 18-month calcium supplementation trial demonstrated a significant increase in radial bone mineral mass in 7-year-old children with calcium intake approximately 300 mg/day (Am J Clin Nutr 1994; 60: 744-50). The persistence of higher bone mass after cessation of calcium supplementation is unknown. This is a follow-up study to investigate the lasting effect of calcium supplementation on bone acquisition. Subjects were 159 Chinese children aged 8.7 years. Distal one-third radial bone mineral content (BMC) and bone width (BW) were measured by single-photon absorptiometry. After 12 months, the significant difference in mean +/- SD percentage radial BMC disappeared between the study and control groups (7.34 +/- 6.77% vs 8.67 +/- 6.46%, p > 0.05). Dietary calcium intakes were similar between the groups. During the supplementation phase, the study group had 17.9% greater BMC gain than that of controls. In the follow-up phase, however, the study group had 16.1% less BMC gain than that of controls. It appears that an increased acquisition rate during the supplementation phase was almost balanced by a reduced acquisition rate during follow-up phase. Moreover, throughout the entire 30-month period, the overall BMC acquisition rates of the study and control groups were 25% and 23.8%, respectively. Hence, the overall acquisition rate of the study group was only 5% higher than that of controls. Therefore, the effect of calcium supplementation on bone mineral gain appears to reflect a transient reduction in bone turnover rate. Longer-term calcium trials are necessary to confirm whether a sustainable higher calcium intake throughout childhood will enhance peak bone mass.
Body Height↗
Cloning and characterization of two groESL operons of Rhodobacter sphaeroides: transcriptional regulation of the heat-induced groESL operon.
The nonsulfur purple bacterium Rhodobacter sphaeroides was found to contain two groESL operons. The groESL1 heat shock operon was cloned from a genomic library, and a 2.8-kb DNA fragment was sequenced and found to contain the groES and groEL genes. The deduced amino acid sequences of GroEL1 (cpn60) and GroES1 (cpn10) were in agreement with N-terminal sequences previously obtained for the isolated proteins (K. C. Terlesky and F. R. Tabita, Biochemistry 30:8181-8186, 1991). These sequences show a high degree of similarity to groESL genes isolated from other bacteria. Northern analysis indicated that the groESL1 genes were expressed as part of a 2.2-kb polycistronic transcript that is induced 13-fold after heat shock. Transcript size was not affected by heat shock; however, the amount of transcript was induced to its greatest extent 15 to 30 min after a 40 degrees C heat shock, from an initial temperature of 28 degrees C, and remained elevated up to 120 min. The R. sphaeroides groESL1 operon contains a putative hairpin loop at the start of the transcript that is present in other bacterial heat shock genes. Primer extension of the message showed that the transcription start site is at the start of this conserved hairpin loop. In this region were also found putative -35 and -10 sequences that are conserved upstream from other bacterial heat shock genes. Transcription of the groESL1 genes was unexpectedly low under photoautotrophic growth conditions. Thus far, it has not been possible to construct a groESL1 deletion strain, perhaps indicating that these genes are essential for growth. A second operon (groESL2) was also cloned from R. sphaeroides, using a groEL1 gene fragment as a probe; however, no transcript was observed for this operon under several different growth conditions. A groESL2 deletion strain was constructed, but there was no detectable change in the phenotype of this strain compared to the parental strain.
Amino Acid Sequence↗
Differential recruitment of B and T cells in coxsackievirus B4-induced pancreatitis is influenced by a capsid protein.
Two genetically similar variants of coxsackievirus B4, CB4-P and CB4-V, cause distinct disease syndromes in mice. A multidisciplinary approach was used to examine the events occurring in situ. The CB4-P variant induced acute pancreatitis, followed by repair of the exocrine tissues, while the CB4-V variant induced chronic pancreatitis, characterized by extensive destruction of the exocrine tissues. Since CB4-V replicated more efficiently than CB4-P in vivo, the more extensive tissue injury associated with CB4-V infection could be explained as the result of a higher level of viral replication. However, the fact that CB4-V replicated more efficiently in a mouse strain that survives infection than in a strain that succumbs to infection suggests that immune-mediated mechanisms as well as viral cytolysis may contribute to pancreatic tissue injury. To address the role of the immune system in virus-induced pancreatitis, the cell types within the inflammatory infiltrate were analyzed by flow cytometry. B cells (34 to 75%) were the most abundant, followed by T cells (10 to 30%), natural killer cells (4 to 8%), and macrophages (0 to 6%). Recruitment (and perhaps proliferation) of B and T cells to the pancreatic tissues was influenced by viral strain. Differential recruitment of T and B cells may reflect altered antigenic sites between CB4-P and CB4-V. The viral sequence that affected T- and B-cell recruitment was identified as a threonine residue at position 129 of the VP1 capsid protein.
Animals↗
Characterization of CD8+ cytotoxic T-lymphocyte responses after genetic immunization with retrovirus vectors expressing different forms of the hepatitis B virus core and e antigens.
Cytotoxic T-lymphocyte (CTL) activity appears to play an important role in resolving hepatitis B virus (HBV) infection, and the ability to induce such responses remains an important goal for developing effective immunotherapeutics. A panel of recombinant retrovirus vectors expressing different forms of the HBV core antigen (HBcAg) or e antigen (eAg) were found to induce antigen-specific major histocompatibility complex-restricted CTL responses in both mice and macaques. In addition, a novel retrovirus vector expressing an HBcAg-neomycin phosphotransferase II (HBc-Neo) fusion protein [LHBc-NEO(6A3)], which allows the measurement of the anti-Neo antibody response as a means of directly tracking biological activity of the vector, was generated. Doses greater than 10(7) CFU were necessary to induce CTL responses in H-2(k) mice. Intramuscular injections with 10(8) CFU of the LHBc-NEO(6A3) retrovirus vector into rhesus monkeys induced HBc/eAg-specific antibody production and CD8+ CTLs. The CTL response from one of the two responder rhesus monkeys was directed against a 9-residue peptide, GELMTLATW, at positions 63 to 71 of the HBc/eAg sequence. The CTL response is long lived, being detectable as late as 16 weeks after immunization, and can be boosted upon reimmunization. The potent ability of recombinant retrovirus vectors to induce HBcAg- and eAg-specific CTL responses may prove beneficial as a therapeutic treatment for chronic hepatitis B infection.
Animals↗
Characterization of humoral and CD4+ cellular responses after genetic immunization with retroviral vectors expressing different forms of the hepatitis B virus core and e antigens.
The humoral and CD4+ cellular immune responses in mice following genetic immunization with three retroviral vectors encoding different forms of hepatitis B virus core antigen (HBcAg) and e antigen (HBeAg) were analyzed. The retroviral vectors induced expression of intracellular HBcAg (HBc[3A4]), secreted HBeAg (HBe[5A2]), or an intracellular HBcAg-neomycin phosphoryltransferase fusion protein (HBc-NEO[6A3]). Specific antibody levels and immunoglobulin G isotype restriction were highly dependent on both the host major histocompatibility complex and the transferred gene. Humoral and CD4+ cellular HBcAg and/or HBeAg (HBc/eAg)-specific immune responses following retroviral vector immunization were of a lower magnitude but followed the same characteristics compared with those after immunization with HBc/eAg in adjuvant. Two factors influenced the humoral responses. First, in vivo depletion of CD8+ cells in HBc-NEO[6A3]-immunized H-2k mice abrogated both HBcAg-specific antibodies and in vitro-detectable cytotoxic T lymphocytes. Second, priming of H-2b mice with an HBc/eAg-derived T-helper (Th) peptide in adjuvant prior to retroviral vector immunization greatly enhanced the HBc/eAg-specific humoral responses to all three vectors, suggesting that insufficient HBc/eAg-specific CD4+ Th-cell priming limits the humoral responses. In conclusion, direct injection of retroviral vectors seems to be effective in priming HBc/eAg-specific CD8+ but comparatively inefficient in priming CD4+ Th cells and subsequently specific antibodies. However, the limited HBc/eAg-specific CD4+ cell priming can effectively be circumvented by prior administration of a recombinant or synthetic form of HBc/eAg in adjuvant.
Animals↗
Retroviral-mediated expression of FIV envelope/Rev induces CD8+ CTL responses in mice.
Recombinant retroviral vectors that express the Env and Rev proteins of feline immunodeficiency virus (FIV) were prepared and analyzed in a mouse model system for their ability to induce antigen-specific CD8+ CTL (cytotoxic T lymphocyte) responses. The ultimate goal of these studies is to develop effective immunogens for CTL induction in the cat. Recombinant Env/Rev retroviral vectors were used to transduce mouse fibroblasts and these cells were then inoculated intraperitoneally into syngeneic BALB/c mice. FIV Env-specific CTL responses were obtained. The potent ability of recombinant retroviral vector-transduced cells to elicit cell-mediated immunity in the mouse model offers the possibility that such delivery systems may serve as therapeutic and/or prophylactic treatments against FIV infection in the cat.
Animals↗
Prenatal diagnosis, pathology, and genetic study of fetus in fetu.
We report the prenatal diagnosis, pathology, cytogenetics, and molecular studies of a retroperitoneal fetus in fetu. Prenatal ultrasonography of the host fetus in the third trimester showed an anencephalic, acardiac mass with identifiable extremities and spine within an intra-abdominal cystic mass. Pathological examination revealed a fetiform mass weighing 20 g with four extremities, digits, vertebral bodies, an oral cavity with developing teeth, primitive male external genitalia, a urinary bladder, a cloaca with an external opening, large intestines, a membranous capsule, and an umbilical cord with one artery, one vein, and Wharton's jelly. Histological examination demonstrated nerve bundles in the fibrocollagenous tissue below the cuboidal surface epithelium of the membranous capsule, and absence of lamina elastica interna and vasa vasorum in the single artery of the umbilical cord. Both the host infant and the fetus in fetu had a normal 46,XY karyotype. Molecular analysis using informative genetic markers showed no genetic difference between the host infant and the fetiform mass. We report this case as an unusual example of fetus in fetu in co-existence with an amnion-like membrane containing nerve bundles and with a well-formed umbilical cord. We demonstrate that fetus in fetu can be diagnosed prenatally if the fetiform mass has well-developed limbs and spine. We emphasize the necessity for suspicion of fetus in fetu when a well-defined encapsulated cystic mass with calcified solid components is detected prenatally in a fetus by ultrasonography.
Adult↗
Memory T cell development in the absence of specific antigen priming.
Numerous studies have shown that memory T cell development is Ag dependent and specific. In the present study, we show that memory responses can be made against an Ag to which there has been no prior exposure. In unimmunized DO11.10 mice, which carry alpha and beta transgenes that encode a TCR specific for OVA, CD45RB(low) memory cells express the transgenic TCR. These cells can be stimulated by OVA to proliferate and perform typical memory functions, such as secrete diverse lymphokines and provide cognate help to B cells, despite the fact that the mice were never exposed to OVA. Thus, memory cells can be generated in the absence of specific Ag. The data also demonstrate that the transgenic TCR-bearing memory T cells possess endogenous TCR alpha-chains, which permit the expression of a second TCR. In DO11.10/RAG(-/-) mice, the endogenous alpha-chains are eliminated, and the T cells can only express the transgenic TCR. In these mice, no memory cells were observed. Thus, it is the additional TCR that appears to drive memory cell generation. Once induced, memory function may be triggered through the transgenic receptor. Since dual TCR-bearing cells have been shown to exist in nontransgenic mice and humans, our results provide evidence that one mechanism for the maintenance of memory responses to a specific Ag is through stimulation of the second TCR by another Ag. Further, these findings have important implications for understanding aberrant immune responses, such as those that occur in autoimmunity.
Animals↗