The pattern of cervical smear abnormalities in marginalised women in Hong Kong.

INTRODUCTION: "Ripple Action" and "WE Stand" are projects co-organised by the Hong Kong Women Doctors Association. The two projects organise free cervical screening for low-income women, new immigrants from Mainland China, and ethnic minority women. The objective of this study was to analyse the pattern of cervical smear abnormalities in these marginalised women. METHODS: The study group consisted of 1189 marginalised women who participated in a free cervical screening campaign, including 324 low-income local Chinese, 540 new immigrants from Mainland China, and 325 ethnic minority women. The comparison group consisted of 1141 local Chinese who attended a well women clinic. The prevalence of cervical smear abnormalities was compared using Chi squared test. RESULTS: In the study group, 42.6% of women had never had a cervical smear. Compared with the comparison group, they had a significantly higher prevalence of cervical smear abnormalities (13.7% vs 1.4%; P<0.001), including atypical smear (10.8% vs 0.5%; P<0.001), low-grade lesion (1.8% vs 0.8%; P=0.036), and high-grade lesion (1.1% vs 0.1%; P=0.002). Logistic regression analysis showed that the strongest predictors for abnormal cervical smear were being South Asian (odds ratio=11.859; 95% confidence interval, 4.635-30.341), South-East Asian (6.484; 3.192-13.171), or new immigrant from Mainland China (6.253; 2.463-15.877). CONCLUSIONS: Marginalised women had a significantly higher prevalence of cervical smear abnormality than the general population and almost half had never had a cervical smear before. Outreach strategies are needed to enrol this population into screening programmes.

Effect of fetal diagnosis on the outcomes of second-trimester pregnancy termination for fetal abnormalities: a pilot study.

OBJECTIVE: To explore whether the outcomes of second-trimester pregnancy termination for fetal abnormalities are affected by fetal diagnoses. METHODS: This was a retrospective review of cases undergoing second-trimester pregnancy termination for the fetal diagnoses of hemoglobin Barts, trisomy 21, and trisomy 18 during the period from 1999 to 2006. The affected pregnancies were terminated by vaginal misoprostol. The outcome measures were: (1) abortion within 24 hours after misoprostol commencement, (2) histology-confirmed incomplete abortion, and (3) experience of significant side effects during termination (temperature over 39 degrees C or need for metoclopramide for vomiting). RESULTS: One hundred and twenty cases were available for analysis. After adjusting for maternal age, parity, history of cesarean delivery, body mass index, gestation, and fetal hydrops, pregnancy termination for trisomy 21 was associated with a higher risk of incomplete abortion than trisomy 18 and hemoglobin Barts (odds ratio 5.25, 95% confidence interval 1.24-22.19, p = 0.024). The chance of abortion within 24 hours and experience of significant side effects were not found to be associated with fetal diagnosis. CONCLUSIONS: Pregnancy termination for trisomy 21 is associated with a higher risk of incomplete abortion. Fetal diagnosis affects the outcome of pregnancy termination.

The effect of gestational age on the outcome of second-trimester termination of pregnancies for foetal abnormalities.

OBJECTIVE: To explore the effect of gestational age on the outcome of second-trimester termination of pregnancies for foetal abnormalities. METHOD: A retrospective study was conducted on 280 pregnancies terminated for foetal abnormalities in the second trimester using vaginal misoprostol. The gestational age at termination was divided into three groups: 13-16 weeks, 17-20 weeks and 21-23 weeks. The likelihood of (1) abortion within 24 h of commencement of misoprostol, (2) incomplete abortion and (3) experiencing significant side effects was compared among these three gestational groups after adjusting for maternal age, parity and body mass index (BMI). RESULTS: Compared to termination after 20 weeks, pregnancy termination for foetal abnormality before 17 weeks of gestation was associated with higher chance of incomplete abortion (OR 2.2, 95% CI 1.07-4.61, p = 0.032) and lower chance of experiencing significant side effects (OR 0.11, 95% CI 0.01-0.91, p = 0.041). CONCLUSION: Women undergoing pregnancy termination for foetal abnormalities in the early second trimester should be informed of possible higher chance of incomplete abortion.

Meconium peritonitis: prenatal diagnosis, postnatal management and outcome.

OBJECTIVES: Prenatal ultrasonography (USS) is a routine screening test for fetal abnormalities. Its accuracy for detecting meconium peritonitis (MP), which may carry high mortality, is important for prenatal counseling. The aim of this study was to assess the accuracy of prenatal USS for diagnosing MP and predicting patient outcomes. METHODS: The prenatal and postnatal medical records of all patients referred to our institutions with confirmed MP were reviewed, with emphasis on prenatal USS findings, results of postnatal investigations, operative findings, outcomes, and possible causes of MP. RESULTS: From January 2000 to November 2004, seven fetuses were confirmed to have MP at birth. Three MP patients (3/7, 43%) were diagnosed prenatally because of USS showing ascites and calcification/dilated or hyperechoic bowel loops. One (1/7, 14.3%) suspected cystic MP was confirmed by prenatal MRI. In the other three cases, USS showed only ascites. All patients had postnatal contrast CT scans. Two patients' CT scans showed persistent intestinal perforation not visible with prenatal USS, and required emergency operations. All patients survived and prospered, and were sweat test negative. CONCLUSIONS: Prenatal USS allows suspected MP babies to be transferred to a tertiary centre for delivery and appropriate management. In this way, the chances of survival of these babies can be excellent if they are not associated with cystic fibrosis (CF). Prenatal MRI can improve the low diagnostic yield of prenatal USS for MP. Postnatal contrast CT scan is required to define persistent intestinal perforation invisible with prenatal USS.

XX-agonadism in a fetus with multiple congenital anomalies.

We report on an 18-week gestation fetus with 46,XX karyotype, gonadal agenesis, meningo-encephalocele, spina bifida, omphalocele, webbing of right upper limb, deformed right clavicle and right sided ribs, absent interventricular septum, hypoplastic aorta, hypoplastic spleen, and single umbilical artery. This case is similar to the one previously described by Kennerknecht et al. in 1997 and may represent a unique syndrome.

Consensus statement on iodine deficiency disorders in Hong Kong.

This article reviews the available data on the study of iodine deficiency disorders in Hong Kong and to discuss the approach towards preventing such disorders in Hong Kong. The importance of iodine and iodine deficiency disorders is described, and the available data on the dietary iodine intake and urinary iodine concentration in different populations of Hong Kong are summarised and discussed. Dietary iodine insufficiency among pregnant women in Hong Kong is associated with maternal goitrogenesis and hypothyroxinaemia as well as neonatal hypothyroidism. Borderline iodine deficiency exists in the expectant mothers in Hong Kong. Women of reproductive age, and pregnant and lactating women should be made aware and educated to have an adequate iodine intake, such as iodised salt, as an interim measure. A steering group involving all stakeholders should be formed to advise on the strategy of ensuring adequate iodine intake, including universal iodisation of salt in Hong Kong. Continuous surveillance of iodine status in the Hong Kong population is necessary.

Factors affecting outcomes of prenatally-diagnosed tumours.

OBJECTIVE: The outcomes of prenatally-diagnosed tumours affect obstetrical management and parental decisions. The present study reviews the factors affecting outcomes for fetuses with prenatally-diagnosed tumours. METHODS: Medical records of all fetuses referred to our institutions with antenatally-diagnosed tumours were reviewed for the type and location of the tumours, results of treatment and/or causes of death. RESULTS: From January 1994 to May 2001, there were 15 fetuses with antenatally- diagnosed tumours: mesoblastic nephroma (MN) (n=2); neuroblastoma (NB) (n=2); cystic hygroma (CH) (n=3); intracranial germ cell tumour (IGCT) (n=2); sacrococcygeal teratoma (SCT) (n=3) and haemangioma (liver, n=2; limb, n=1). One mother had termination of pregnancy for her fetal SCT. Three mothers had Caesarean section for large fetal heads (CH, n=2; IGCT, n=1). Three fetuses died; two with IGCT and one with SCT, who died of heart failure. Two newborns with CH needed emergency intubation and, later, one of them had tracheostomy. One baby had cardiac failure resulting from a lower limb haemangioma and needed drug therapy. All solid tumours (MN, NB, SCT) of the live births had no recurrence after surgery with or without adjuvant chemotherapy. CONCLUSION: Prenatally-diagnosed tumours without any other associated abnormality cause morbidity and mortality because of their location and vascularity. Solid tumours are relatively benign.

Quantitative polymerase chain reaction for the rapid prenatal diagnosis of homozygous alpha-thalassaemia (Hb Barts hydrops fetalis).

A quantitative polymerase chain reaction (Q-PCR) method based on the TaqMan technology has been devised for the prenatal diagnosis of homozygous alpha*-thalassaemia (south-east Asian type deletion). Primers and TaqMan probes were designed to specifically amplify an alpha*-thal chromosomal fragment or a normal alpha-chromosomal fragment. Variations in input target DNA in individual sample wells were normalized by the simultaneous amplification of a beta-actin gene fragment and results expressed as a ratio to that of beta-actin. There was no overlap of the data between the homozygous alpha*-thal, alpha*-thal and normal subjects. Up to 5% maternal DNA (alpha*-thal) contamination did not affect the specificity of the result. In 31 prenatal diagnoses, the result using Q-PCR compared favourably with the gold standard of Southern hybridization of alpha-genes.

Universal screening of human immunodeficiency virus infection in pregnant women in Hong Kong: prospective study.

OBJECTIVE: To evaluate universal screening with an opt-out approach of pregnant women for human immunodeficiency virus infection. DESIGN: Prospective study. SETTING: Regional hospital, Hong Kong. PATIENTS: All women booked or delivered in Kwong Wah Hospital from 1 January 1999 to 30 November 1999 were recruited. MAIN OUTCOME MEASURES: Numbers of women who received the human immunodeficiency virus antibody screening test, refused the test (and the reasons why), tested positive, and tested positive with confirmation by immunoblot study. RESULTS: A total of 5597 women were recruited and 5459 screening tests performed in this study. Of the 16 screened positive cases, three were confirmed by immunoblot study. The overall acceptance rate for the test was 97.5%. The acceptance rate among the 5191 women recruited through the hospital's booking clinic was not significantly different from that among the 406 women who did not go through the hospital's booking clinic (97.6% versus 96.6%). CONCLUSION: Universal screening of pregnant women for human immunodeficiency virus infection with an opt-out approach is practical, feasible, and clinically acceptable in Hong Kong.

Ductus venosus Doppler study in fetuses with homozygous alpha-thalassemia-1 at 12 to 13 weeks of gestation.

OBJECTIVE: Fetuses affected by homozygous alpha-thalassemia-1 are anemic from the first trimester of pregnancy. We investigated ductus venosus Doppler velocimetry in these affected fetuses at 12-13 weeks of gestation. DESIGN: Prospective observational study. SUBJECTS: Women referred for the prenatal diagnosis of homozygous alpha-thalassemia-1 before 14 weeks of gestation. METHODS: All fetuses underwent pulsed Doppler investigations following color flow mapping at 12 or 13 weeks of gestation. Homozygous alpha-thalassemia-1 was diagnosed by DNA or hemoglobin study. The ductus venosus Doppler indices--Vmax (peak velocity during ventricular systole), Vmin (minimum forward velocity during atrial systole), TAMX (time-averaged maximum velocity), PIV (pulsatility index for veins, Vmax-Vmin/TAMX), PLI (preload index, Vmax-Vmin/Vmax) and Vmax/Vmin ratio--were compared between the affected fetuses and fetuses unaffected by homozygous alpha-thalassemia-1. RESULTS: Between June 1998 and October 1999, 102 eligible women were recruited. Fetal ductus venosus Doppler study was successful in 96 pregnancies (94%). Of these, 20 fetuses were affected by homozygous alpha-thalassemia-1. None of them showed hydropic changes at the time of Doppler study. The affected fetuses had significantly higher ducts venosus Vmax (30% increase), Vmin (50% increase) and TAMX (20% increase) and significantly lower Vmax/Vmin ratio, PIV and PLI values. CONCLUSION: Fetuses affected by homozygous alpha-thalassemia-1 at 12-13 weeks had increased forward flow velocities in the ductus venosus throughout the cardiac cycle. The increase of venous return is consistent with our previous report of cardiac dilatation and an increase of cardiac output in the affected fetuses at this stage as a compensatory mechanism for anemia and hypoxia. However, extensive overlap of the ductus venosus Doppler indices between affected and unaffected fetuses precludes its use in predicting anemia at 12-13 weeks.

Echogenic bowel in fetuses with homozygous alpha-thalassemia-1 in the first and second trimesters.

OBJECTIVE: Fetal echogenic bowel has been observed in fetuses with meconium peritonitis, cystic fibrosis, aneuploidy, congenital viral infection and intrauterine growth restriction. The pathogenesis of echogenic bowel is unknown, but it may be attributed to bowel ischemia. Fetuses affected by homozygous alpha-thalassemia-1 are severely anemic and hypoxic. We investigated the incidence of echogenic bowel in these hypoxic fetuses in the first and second trimesters. DESIGN: Prospective observational study. SUBJECTS: Women referred for the prenatal diagnosis of homozygous alpha-thalassemia-1 before 24 weeks' gestation. METHODS: All subjects had one or more abdominal and/or vaginal ultrasound examination between 12 and 24 weeks' gestation. Echogenic bowel was diagnosed if the bowel appeared either isoechogenic or more echogenic than the bone. RESULTS: Between March 1997 and July 1998, 126 pregnancies were studied. Thirty-six fetuses were confirmed to be affected by homozygous alpha-thalassemia-1, and 11 of them (31%, 95% CI 16-48%) had echogenic bowel. These observations were made before the invasive test results were available. None of the fetuses unaffected by homozygous alpha-thalassemia-1 had echogenic bowel. CONCLUSION: There is a strong association between homozygous alpha-thalassemia-1 and echogenic bowel. The pathogenesis is unknown. Speculations include bowel hypoperistalsis or bowel wall edema due to severe anemia and hypoxia.

Nuchal translucency in fetuses affected by homozygous alpha-thalassemia-1 at 12-13 weeks of gestation.

OBJECTIVE: Fetuses affected by homozygous alpha-thalassemia-1 are anemic in the first trimester. We studied their nuchal translucency (NT) measurements at 12-13 weeks of gestation. METHODS: Nuchal translucency was measured prospectively in fetuses at risk of homozygous alpha-thalassemia-1. Measurements of those fetuses subsequently confirmed to be affected by homozygous alpha-thalassemia-1 but with a normal karyotype were compared to those of 440 controls. The controls were from the general obstetric population who had NT measurements at 12 or 13 weeks with known normal outcome. All the NT measurements were expressed as multiples of the median (MoM) for the gestational day. RESULTS: Between 1996 and 1998, 94 at-risk pregnancies were studied. Of these, 32 were subsequently confirmed to be affected by homozygous alpha-thalassemia-1. Chromosome study was not carried out in three cases and these were excluded from the analysis. Nuchal translucency MoMs for cases and controls were found to fit a log Gaussian distribution. The log means (standard deviation) for case and control NT MoM were 0.075 (0.156) and -0.0019 (0.091), respectively. The median NT MoM (95% CI) for cases was 1.19 (1.08-1.62) and was significantly higher than that of the controls (p < 0.001). However, there was extensive overlap of NT between cases and controls. CONCLUSION: Overall, there was a 19% increase in NT MoM in fetuses affected by homozygous alpha-thalassemia-1. This represents a difference of only 0.3-0.4 mm, which is clinically insignificant. This finding indirectly suggests that the increased NT in trisomic fetuses cannot be explained by fetal anemia. Conversely, the presence of increased NT in a fetus at risk of homozygous alpha-thalassemia-1 should alert one to the possibility of chromosomal abnormality rather than being attributed to fetal anemia.

Cardiac blood flow studies in fetuses with homozygous alpha-thalassemia-1 at 12-13 weeks of gestation.

OBJECTIVE: Fetuses affected by homozygous alpha-thalassemia-1 develop anemia as early as the first trimester. Our objective was to study hemodynamic indices in affected fetuses at 12-13 weeks of gestation to determine whether these would be useful in the prediction of anemia. DESIGN: Prospective observational study. SUBJECTS: Women referred before 14 weeks of gestation for the prenatal diagnosis of homozygous alpha-thalassemia-1. METHODS: Transabdominal and/or transvaginal Doppler sonography was performed to measure the flow velocities in the fetal ascending aorta and pulmonary artery at 12-13 weeks. The Doppler indices were compared between those that were subsequently confirmed to be affected by homozygous alpha-thalassemia-1 and those that were unaffected. RESULTS: Between June 1997 and April 1998, 60 eligible women were recruited. Doppler examination was successful in 58 fetuses. Of these, 22 were subsequently confirmed to be affected by homozygous alpha-thalassemia-1. The diagnosis was made by chorionic villus sampling and DNA analysis in two affected fetuses and by cordocentesis and hemoglobin evaluation in 20 affected fetuses. Hemoglobin concentrations could be measured in ten fetuses and these ranged from 4 to 8 g/dl. The affected fetuses had significantly higher peak velocities at the pulmonary valve and ascending aorta and a larger inner diameter of the pulmonary valve than that in unaffected fetuses. The total cardiac output was increased by one-third in affected fetuses and was mainly due to an increase of the right-side cardiac output. CONCLUSION: In the early stage of anemia, the fetus responds mainly by increasing its right-side cardiac output. However, there is extensive overlap of the values of cardiac output between the affected and the unaffected fetuses, precluding its use in the prediction of anemia.

Prenatal ultrasonographic prediction of homozygous type 1 alpha-thalassemia at 12 to 13 weeks of gestation.

We determined the feasibility of prenatal prediction of type 1 homozygous alpha-thalassemia at 12 to 13 weeks of gestation by either abdominal or vaginal (or both) ultrasonographic examination to measure the fetal cardiothoracic ratio in 135 at-risk pregnancies. Forty-three fetuses were affected by homozygous type 1 alpha-thalassemia. The mean cardiothoracic ratio was significantly larger than that of the unaffected fetuses (0.54 vs 0.45, P <.0005), with no overlap between the 2 groups. A cardiothoracic ratio cutoff point of >/=0.5 was 100% sensitive and specific for disease.

Prenatal sonographic diagnosis of conjoined twins in the first trimester: two case reports.

Conjoined twins are a rare occurrence. We present two cases of conjoined twins diagnosed by ultrasound examination at 8 and 13 weeks' gestation, respectively. These cases demonstrated the possibility of making an accurate diagnosis of conjoined twins and delineating the extent of organ sharing in the first trimester.

Local delivery of interleukin 4 by retrovirus-transduced T lymphocytes ameliorates experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory autoimmune disease of the central nervous system which serves as a model for the human disease multiple sclerosis. We demonstrate here that encephalitogenic T cells, transduced with a retroviral gene, construct to express interleukin 4, and can delay the onset and reduce the severity of EAE when adoptively transferred to myelin basic protein-immunized mice. Thus, T lymphocytes transduced with retroviral vectors can deliver "regulatory cytokines" in a site-specific manner and may represent a viable therapeutic strategy for the treatment of autoimmune disease.

Induction of myelin basic protein-specific experimental autoimmune encephalomyelitis in C57BL/6 mice: mapping of T cell epitopes and T cell receptor V beta gene segment usage.

Early studies of murine experimental autoimmune encephalomyelitis (EAE) induced with myelin basic protein (MBP) divide various mouse strains into either "susceptible" or "resistant" phenotypes. Resistance is defined as lack of encephalitogenic responses after active immunization or adoptive transfer. It is now becoming clear that this unresponsiveness is not due to the inability of T cells to recognize MBP in the context of major histocompatibility complex (MHC) gene products. Using various manipulations, many laboratories are able to induce severe EAE in these strains. We previously reported that a combination of adoptive transfer and subsequent challenge of the recipients with MBP could overcome the resistance in many mouse strains (Shaw et al.: J Neuroimmunol 39:139-150, 1992). This approach now enables us to identify the encephalitogenic epitope and T cell receptor V beta usage in a prototype strain, C57BL/6 (B6). Pepsin-digested MBP fragments first located a major T cell epitope in a polypeptide containing residues 44-88. Overlapping synthetic peptides narrowed this epitope to p60-80. Truncated peptides from the carboxyl- or amino-terminus further mapped a minimal peptide to p67-76. This encephalitogenic epitope appears to be unique to B6 mice. Independent encephalitogenic T cell clones specific for this epitope were also generated. Of six such clones analyzed, five different TCR V beta's were found. Whether unbiased usage of encephalitogenic TCR V beta gene segments in B6 mice is related to its EAE resistant phenotype is not clear at this point.

Experimental allergic encephalomyelitis. T cell trafficking to the central nervous system in a resistant Thy-1 congenic mouse strain.

BACKGROUND: The understanding of recognition events that underlie the migration of antigen-specific T cells to a target organ during immune-mediated damage will be integral to the therapy of a number of human conditions of proven or suspected autoimmune etiology. In experimental allergic encephalomyelitis (EAE), the laboratory model of the human demyelinating disease, multiple sclerosis, previous studies have concentrated on susceptible strains and have shown that myelin-specific T cells play an early, key role in central nervous system (CNS), lesion formation. Not known in this model is whether in EAE-resistant strains, similar antigen-specific T cells possess the ability to recognize CNS endothelium and infiltrate the CNS. EXPERIMENTAL DESIGN: Myelin basic protein (MBP)-responsive T cells derived from mice of the C57BL/6 strain (bearing the Thy-1.2 allele) were adoptively transferred to the Thy-1.1 congenic strain C57BL/Ka. Some recipients were given a subsequent challenge with MBP in adjuvant, a protocol recently shown to break resistance in this strain and cause EAE. On the basis of the difference in Thy-1 allele, T cell trafficking was followed in this EAE-resistant congenic strain following the different sensitization protocols. RESULTS: In C57BL/Ka mice receiving adoptively transferred C57BL/6 cells followed by MBP challenge, donor MBP-responsive Thy-1.2+ lymphocytes were detected by immunocytochemistry in the Thy-1.1 host CNS and also in peripheral lymphoid organs. In mice given MBP-sensitized cells without additional antigen challenge, although Thy-1.2+ cells were found in the spleen and lymph nodes, similar cells could not be found in the CNS, and animals displayed neither clinical nor pathologic signs of EAE. Donor T lymphocytes appeared in the host CNS with clinical onset, 10 to 14 days after challenge. When mice went into remission, Thy-1.2+ lymphocytes could not be found in the CNS, but were still present in peripheral lymphoid organs up to 3 months after challenge. From the total number of infiltrating cells, T cell receptor-alpha beta+ cells constituted 27% in perivascular cuffs, 15% in meninges, and 13% in the parenchymal infiltrates in the spinal cord. Thy-1.2+ cells contributed up to about 40% of total T cell receptor-alpha beta+ lymphocytes. Approximately 60% of all infiltrating T cells expressed L3T4 (helper/inducer), whereas 18% expressed Lyt-2 (suppressor/cytotoxic). The majority of infiltrating cells were memory and activated cells expressing on their surface Pgp-1 and CD 25. Immunostaining for cytokines showed that the majority of infiltrating cells belonged to the TH1 subset and contained interferon-gamma and tumor necrosis factor-alpha, while a minority were positive for interleukin-4. CONCLUSIONS: These results suggest that: (a) T lymphocytes from an EAE-resistant strain of mouse are capable of homing to the CNS; (b) T lymphocytes from an EAE-resistant strain express phenotypic characteristics, activation, memory, and cytokine profiles similar to infiltrating cells derived from susceptible strains; and (c) the presence of donor T cells in the recipient CNS correlates with clinical and histopathologic signs of EAE.

Homing of T cells to the central nervous system throughout the course of relapsing experimental autoimmune encephalomyelitis in Thy-1 congenic mice.

Chronic relapsing experimental allergic encephalomyelitis (EAE) was induced in Thy-1.1 congenic SJL/J mice by the adoptive transfer of myelin basic protein (MBP)-responsive lymph node cells from Thy-1.2 SJL/J mice. The Thy-1 congenic mouse strain was constructed on the SJL (Thy-1.2) background by the initial cross with the AKR (Thy-1.1) strain and does not reject Thy-1.2+ T cells. Quantitative immunocytochemical analysis of the central nervous system (CNS) of Thy-1.1 recipients showed preferential trafficking of Thy-1.2+ T cells to the meninges and white matter, beginning prior to onset of clinical signs. At 7 days post-transfer (dpt), Thy-1.2+ donor cells constituted 2.5% of the infiltrating cells and reached peak values (ca. 10%) during the first attack. At later stages (up to ten relapses), Thy-1.2+ T cells constituted 2-5% of the infiltrate. In control mice injected with irrelevant antigen-stimulated Thy-1.2+ T cells, only the occasional Thy-1.2+ T cell could be demonstrated up to 14 dpt. This is the first study showing unequivocally the presence of MBP-stimulated, adoptively transferred T cells within the CNS of recipients throughout the course of EAE, particularly during later relapsing stages. These results indicate that the persistent presence of antigen-specific T cells may be required for the recruitment of non-CNS antigen-responsive immune cells.