Biomedical subjects

G Lombardi

Publications and source records attributed to G Lombardi.

At least 37 records · Page 2Linked to original sources

PubMed2005

Associated hormonal decline in aging: is there a role for GH therapy in aging men?

Aging is associated with decline in the somatotroph axis, a decline that has been considered to cause many of the catabolic sequelae of normal aging. Consequently, IGF-I levels decline progressively: this mainly reflects the impaired GH secretion, but decline in gonadal sex steroids and malnutrition also play a role. Decreases in GH secretion may partially explain the age-related changes in metabolism, bones, muscles, cardiovascular system, central nervous system, the immune system and sense of well-being. Normal aging and GH deficiency (GHD) share several clinical signs and symptoms: the endocrine pattern of aging is, however, distinct from the decrease of GH and/or IGF-I levels associated with hypopituitarism. Owing to clinical similarities between aging and GHD, the relative GH insufficiency of elderly subjects has been postulated as one important factor contributing to their frailty. However, it is currently unclear whether treatment with exogenous GH, or IGF-I can retard or reverse age-related changes in body structure and function. Several studies enrolling healthy elderly subjects showed that GH treatment was followed by increase of lean mass, decrease of fat mass and improvement of bone turnover, but other studies failed to confirm these data. The treatment with natural or synthetic GH secretagogues, that could represent a physiological approach to restore the GH and IGF-I secretion, requires further investigations. In conclusion, there is not sufficient evidence for a clear therapeutic role of rhGH, IGF-I, and secretagogues in aging. Further studies are needed to evaluate the real benefit of somatotropic treatment in aging men.

Aged↗

PubMed2005

Severe systemic complications of acromegaly.

It is well accepted that mortality in acromegaly is increased because of cardiovascular and respiratory diseases while neoplastic complications account less to mortality. Amongst different cardiovascular complications the most frequent is biventricular hypertrophy, which occurs independently of hypertension and metabolic complications that, in turn, aggravate the cardiomyopathy. Diastolic and systolic dysfunction develops in a variable number of patients, depending on age and disease duration. Other cardiac disorders, such as arrhythmias, valve disease, hypertension, atherosclerosis and endothelial dysfunction have been less characterized but all appear to be present in acromegaly, depicting the so called "acromegalic cardiomyopathy". The best characterized respiratory disease is the sleep apnea. Ventilatory dysfunction recognizes bony changes of thoracic cage and lung overgrowth as relevant pathogenetic factors. Earlier evidences that patients with acromegaly have an increased risk of developing malignancies have become more realistic in recent years. Most studies have reported an increased risk of colonic polyps, which more frequently recur in patients not controlled after treatment. Malignancies in other organs have also been described, but less convincingly than at the gastrointestinal level and are not a main cause of mortality. Bone changes are also feature of the disease. They involve theoretically all bones and, particularly, the appendicular and the axial skeleton. Patients with long-standing disease are more prone to develop degenerative changes. Control of acromegaly by surgery or pharmacotherapy, especially by somatostatin analogs, improves cardiovascular morbidity and sleep apnea. There is still no demonstration that improvement of different complications corresponds a reduction in mortality.

Acromegaly↗

PubMed2005

[Congenital cytomegalovirus infection].

The cytomegalovirus (CMV) is responsible for the most common congenital infection and represents the most important cause of mental disability and non hereditary sensorineural deafness in infants. One percent to 5% of women show symptoms of infection during pregnancy. Forty thousand newborns are affected by this infection in the United States every year, at a cost of 1.9 billion dollars; in Italy, approximately 5,500 infected newborns are expected each year, including 350 in Lombardia alone. In 90% of the cases, the infected newborns present no symptoms at birth, but, in 10% to 15% of these cases, they are not immune to future manifestations of the infection. Ten percent of newborns with congenital infection, however, show symptoms that lead to a strongly unfavourable prognosis. The authors describe the most important pre and post natal diagnostic findings and emphasize the importance of counseling in this pathology. They also point out the least frequent clinical manifestations of the infection in newborns, which can cause problems of differential diagnosis. In light of the most recent literary data, the article outlines the most recent therapeutic schemes as well as their effectiveness. Lastly, the authors discuss the sequels of the congenital infection, which can present themselves in infected newborns even after a long period of time. This corresponds to one of the most important aspects of the topic and the authors propose a follow-up program that applies to those children until the age of 6. There is currently no effective or safe vaccine for the CMV, therefore hygienic-health measures constitute the principal form of prevention of the CMV congenital infection, which represents a significant problem for newborns, their families, and society.

Antiviral Agents↗

PubMed2005

The acromegalic arthropathy.

Since the initial definition of acromegaly over 100 yr ago, extraordinary efforts have been made to control GH levels and the pituitary tumor. Criteria of cure have been evolving constantly and all previous statements should be revised according to modern criteria of disease control. Arthropathy is undoubtedly the most important cause of morbidity and functional disability of acromegaly, and bone alterations are highly characteristic of this syndrome. They involve theoretically all bones and, particularly, the appendicular and the axial skeleton. Radiographic changes at different joint sites are more common than symptoms related to their involvement. There is a progression in the acromegalic arthropathy, resembling that described for the acromegalic cardiomyopathy or for the acromegalic features at other organs, such as thyroid, breast and prostate. At early stage, cartilage hypertrophy predominates, and then degenerative changes start until osteoarthritis features occur. Arthropathy can be reversed by normalizing GH and IGF-I levels only at the initial stage. If the disease is left untreated for long time, the osteo-articular sequelae cannot be modified by any treatment of acromegaly.

Acromegaly↗

PubMed2005

Somatopause: dismetabolic and bone effects.

The physiological changes that the human body undergoes during aging are similar to those observed in GH deficiency (GHD). Early changes of aging are represented by increased fat mass, increased cardiovascular risk, reduced muscle mass and strength, reduced exercise tolerance, thinned skin, decreased strength and impaired quality of life. These observations led to hypothesize that the elderly could be GH deficient and would benefit from GH treatment. However, the effects of GH treatment in healthy elderly subjects by randomized and controlled studies are less promising than initially hypothesized. The etiopathology of age-related bone loss is multifactorial including menopause, andropause, somatopause and secondary hyperparathyroidism. GH has multiple effects on bone, either direct or mediated by IGF-I, stimulating osteoblast proliferation as well as osteoclast differentiation. Consequently, decline in GH secretion reduces bone turnover that causes osteopenia in young adults, but it has been hypothesized that it could protect against fractures in elderly subjects. The increase of bone remodeling achieved by GH therapy may be helpful in elderly men and women who have severely decreased bone turnover and impaired osteoblastic function. In conclusion, the endocrine pattern of aging is distinct from the decrease of GH/IGF-I levels associated with hypopituitarism. However, GH plays a role in metabolism and bone physiology throughout the human life span, although there is insufficient evidence for a clear therapeutic role of rhGH in aging. Thus, more data are needed to define the effects of somatopause to identify who could potentially benefit from the effects of somatotropic treatment.

Adult↗

PubMed2005

New perspectives in the medical treatment of acromegaly.

Currently available medical treatment of acromegaly includes dopamine agonists, slow release formulation of somatostatin analogues and pegvisomant, a GH-receptor antagonist. Dopamine agonists are well tolerated, not expensive but poorly effective. Somatostatin analogues are highly effective in 60-70% of patients based on the receptor profile of individual tumors. Pegvisomant is reported to normalize IGF-I levels in nearly the totality of the patients, but is devoted of tumor shrinking effect. In a preliminary study in patients with acromegaly, a new somatostatin analogue with affinity to four of the five somatostatin receptors (SOM230) was shown to be similarly effective as octreotide in some patients and more effective than octreotide in other patients. Moreover, new molecules with selective activity on the somatostatin receptor type 2, or 5, or 1 have been reported in vitro to strongly suppress GH secretion. Other new promising alternatives are the chimeric compounds with both somatostatin receptor and dopamine receptor binding. These drugs have been also shown to possess strong GH-inhibitory activity in primary cultures from GH-secreting adenomas. These drugs are the future perspectives in the treatment of patients with GH-secreting or GH/PRL-secreting tumors.

Acromegaly↗

PubMed2004

Anti-Saccharomyces cerevisiae mannan antibodies in inflammatory bowel disease: comparison of different assays and correlation with clinical features.

BACKGROUND: Anti-Saccharomyces cerevisiae mannan antibodies have been proposed as a new serological marker associated with Crohn's disease. However, their clinical value is still unclear; furthermore, a standardization of anti-S. cerevisiae mannan measurements is lacking. AIM: In this study, we aimed to assess the correlation between anti-S. cerevisiae mannan detection and specific clinical features in Crohn's disease and ulcerative colitis. Moreover, we tested the concordance of four different anti-S. cerevisiae mannan assays. MATERIALS AND METHODS: Serum samples from 196 patients with Crohn's disease, 197 patients with ulcerative colitis and 100 unrelated healthy controls were tested for anti-S. cerevisiae mannan with a standard enzyme-linked immunosorbent assay method (Lille) by one of the authors (VP). Subsequently, 60 randomly selected serum samples (27 Crohn's disease, 28 ulcerative colitis and five healthy controls) were tested for anti-S. cerevisiae mannan with three different commercial kits. RESULTS: With the Lille assay, anti-S. cerevisiae mannan were detected in 100 of 196 patients with Crohn's disease (51%; P < 0.0001 vs. controls), 32 of 197 patients with ulcerative colitis (16%; P < 0.02 vs. controls), and six of 100 controls (6%). No correlation between presence of anti-S. cerevisiae mannan and specific clinical features was found in both ulcerative colitis and Crohn's disease patients. The percentages of anti-S. cerevisiae mannan detected with four different assays ranged from 28 (Bouty) up to 43% (Inova), but these differences did not reach statistical significance. The concordance rate of anti-S. cerevisiae mannan detection in the four assays was very low (11 concordant results of 60 samples, 18.3%) (k = 0.15). No improvement of the concordance rate was obtained by modifying the suggested cut-off values (k = 0.20). CONCLUSION: In this study, we confirm that anti-S. cerevisiae mannan are significantly more frequent in Crohn's disease patients compared with ulcerative colitis patients (P < 0.0001) and controls. However, no correlation with clinical features was found in both ulcerative colitis and Crohn's disease. The low prevalence of anti-S. cerevisiae mannan, at least in our population, and the low concordance rate between different assays, makes the clinical role of this marker questionable.

Adolescent↗

PubMed2004

Expression and function of somatostatin receptor subtype 1 in human growth hormone secreting pituitary tumors deriving from patients partially responsive or resistant to long-term treatment with somatostatin analogs.

The role of somatostatin (SS) receptor subtype 1 (SSTR(1)) in mediating the inhibitory effect of SS on growth hormone (GH) secreting pituitary tumors has been recently demonstrated. In the present study, we evaluated the effect of the selective SSTR(1) agonist BIM-23745 on in vitro GH secretion in GH-secreting pituitary tumor cells, deriving from patients resistant or partially responsive to octreotide long-acting release (octreotide-LAR) or lanreotide therapy in vivo and expressing SSTR(1) mRNA. In addition, the inhibiting effect of BIM-23745 on the GH secretion was compared with that of octreotide. Our data demonstrate that (1) SSTR(1) receptor was present in 56.25% (9/16) of the GH-secreting adenomas examined; (2) in all GH-secreting pituitary tumors that expressed SSTR(1), BIM-23745 significantly inhibited GH secretion in vitro, and (3) when SSTR(1) subtype was present in tumors from patients resistant to octreotide-LAR or lanreotide therapy, BIM-23745 was able to inhibit the in vitro GH secretion. In conclusion, the results of the current study suggest that SS analogs selective for the SSTR(1) may represent a further useful approach for the treatment of acromegaly in patients resistant or partially responsive to octreotide-LAR or lanreotide treatment in vivo.

Acromegaly↗

PubMed2004

Long-term efficacy of doxazosin plus atenolol in the management of severe and sustained arterial hypertension and reversibility of the cardiac damage induced by chronic cathecolamine excess. A case report in a young girl with recurrent, functioning paraganglioma.

Herein we report on a young girl with recurrent, functioning paraganglioma of the organ of Zuckerkandl and severe and sustained arterial hypertension (systolic pressure >200, diastolic pressure >120 mmHg); with evidence of cardiac damage induced by chronic cathecolamine excess. She promptly and steadily improved after the institution of doxazosin (6 mg/day) plus atenolol (50 mg bid) treatment. This case demonstrates that a correct therapeutic strategy in the long-term management of patients with inoperable catecholamine-producing neuroendocrine tumors (pheochromocytomas and paragangliomas) can maintain arterial pressure in the normal range and reverse the cardiac damage induced by chronic cathecolamine excess.

3-Iodobenzylguanidine↗

PubMed2004

Is ovulation induction still a therapeutic problem in patients with polycystic ovary syndrome?

Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases affecting women of fertile age, and is characterized by hyperandrogenism, chronic anovulatory cycles and oligomenorrhea or amenorrhea. Given the repercussions of chronic anovulation on sterility, PCOS is a heavy social burden. Here we describe the procedures used to induce ovulation in PCOS patients, the surgical approach and medical treatments that are still being experimented.

Aromatase Inhibitors↗

PubMed2004

Adrenal adenoma and normal androgen levels in a young woman with polycystic ovaries: a case of idiopathic hirsutism?

A case of unusual combination of polycystic ovaries (PCO), adrenal non-functioning adenoma and severe hirsutism in a young woman from Southern Italy is reported here. A 18-yr-old woman was referred to our Department because of oligomenhorrea, acne and severe hirsutism. During evaluation of the cause of her symptoms, PCO and small left adrenal adenoma were revealed. Although adrenal androgen excess has been shown to dysregulate the hypothalamic-pituitary-gonadal axis, causing PCO-like syndrome, normal circulating androgen values were found. Androgens and cortisol levels were completely suppressed by low-dose dexamethasone test, excluding autonomous steroid secretion by the adrenal mass. Normal response of cortisol and adrenal androgens to corticotropin stimulation test permitted the exclusion of functional adrenal hyperandrogenism. Despite normal LH/FSH ratio, anovulatory cycles were revealed by persistently low progesterone values. Glucose and insulin response to oral glucose tolerance test did not differ from those of normal population. The patient showed an improvement of acne and hirsutism on therapy with estro-progestins (EP). In conclusion, despite normal pattern of serum androgens and LH/FSH ratio, this patient had anovulatory cycles and good response to the EP treatment. These findings suggest that ultrasonography evidence of PCO together with anovulatory cycles contributed to her clinical picture whereas adrenal adenoma seemed to have no relevant role. This case report underlines the need of cautious interpretation of imaging results and clinical signs of severe hirsutism, reminding one that the true cause of a medical problem may not be the most evident.

Acne Vulgaris↗

PubMed2004

Different anal pressure profiles in patients with anal fissure.

BACKGROUND: A consistent debate exists about the association between anal fissure and hypertonic anal canal. The aim of this study was to determine if the manometric findings in patients with chronic anal fissures varied according to the topography of the fissure. PATIENTS AND METHODS: Seventy-three outpatients (52 men, 71%) with chronic anal fissures and nine healthy volunteers (5 men, 55%) were examined. Patients were classified according to the topography of the anal fissures: posterior midline (group A), anterior midline (group B), and lateral position (group C). We use computerized anorectal manometry to evaluate anal resting pressure, maximal voluntary contraction, recto-anal inhibitory reflex, rectal sensations and rectum compliance. RESULTS: In Group A, the mean pressure was higher than that of controls (p<0.05), and the resting pressure 2 cm from anal verge was higher than that of other groups and controls (p<0.05). Normotonic anal canal was found in 49.1% of patients in group A, in 66% of those in group B and in 57.1% of those in group C. Four elderly patients (7%) of group A had a hypotonic anal canal. No differences were found regarding maximal voluntary contraction, recto-anal inhibitory reflex, rectal sensations and rectum compliance between patients and controls. CONCLUSIONS: Patients with chronic anal fissures may have several anal pressure profiles. The anal canal is often normotonic. Fissures with hypertonic or normo-hypotonic anal canal need different therapies.

Adolescent↗

PubMed2004

The role of somatostatin receptors in the medical treatment of acromegaly.

Somatostatin is a hypothalamic inhibitor of pituitary growth hormone secretion and cell proliferation, binding to five distinct receptor subtypes (sstr1-5). Since native somatostatin has a short half-life, somatostatin analogues with a longer half-life have been developed for therapeutic purposes. Octreotide and lanreotide are currently available for treatment of acromegaly, binding with high-affinity sstr2 and sstr5. Octreotide, the first somatostatin analogue used in the medical therapy of acromegaly, was initially given subcutaneously at doses of 100-500 microg three times daily. The introduction of new depot formulations, such as octreotide long-acting release, slow-release lanreotide and lanreotide-autogel, improved patients compliance of long-term therapy, overcoming the inconvenience of multiple daily administration. The treatment with somatostatin analogues induces biochemical control and tumour shrinkage in about 50-70% and 30-60% of patients with acromegaly, respectively. However, the efficacy of this therapy lies on an adequate expression of sstr2 and sstr5 on tumor cells. In the past, somatostatin receptor expression was tested in vivo by (111)In-diethylenetriaminepentaacetate-D-Phe-octreotide scintigraphy: this method has been abandoned since normal pituitary tissue can be visualised by (111)In-diethylenetriaminepentaacetate-D-Phe-octreotide scintigraphy. Currently, the somatostatin receptorial profile can be characterised by autoradiography, molecular biology techniques and immunohistochemistry on surgically removed tumor tissue. These methods may offer an individualised approach sparing patients from unnecessary treatment.

Acromegaly↗

PubMed2004

Screening a coastal population in Southern Italy: iodine deficiency and prevalence of goitre, nutritional aspects and cardiovascular risk factors.

BACKGROUND AND AIM: To evaluate the prevalence of goitre by means of urinary iodine excretion, palpatory and ultrasonographic thyroid examinations in a heterogeneous population living by the sea. METHODS AND RESULTS: We used a special self-administered questionnaire to evaluate thyroid size, iodine intake, eating habits and cardiovascular risk factors in 600 subjects with a mean age of 45 +/- 17 years: 253 men (42.3%) and 347 women (57.7%). Urinary iodine excretion was low (72.1 +/- 15.7 microg/L; median 71.2) and associated with ultrasonographic evidence of an enlarged thyroid (16%) or structural thyroid abnormalities (30%), thus allowing us to define the Salerno Gulf as a mild-moderate area of endemic goitre. All of the subjects ate a Mediterranean diet, with a mean of two portions of fish/week. The cardiovascular risk factors considered were obesity, cigarette smoking, hypertension, hypercholesterolemia, hypertriglyceridemia and diabetes, the prevalences of which were in line with those reported in other studies of similar age-matched populations. CONCLUSIONS: The moderate intake of fish and the consumption of a Mediterranean diet did not prevent goitre. Iodine deficiency and subsequent goitre endemia are also present at sea level, probably because of a diet based on local products grown on soil with a low iodine content or possible seawater, soil and air environmental pollution that may interfere with the availability of iodine. The assessment of iodine deficiency should therefore involve the entire population and not only subjects living far from the sea.

Adult↗

PubMed2004

Imatinib inhibits the activation and proliferation of normal T lymphocytes in vitro.

The ABL tyrosine kinase inhibitor imatinib mesylate is highly effective in the treatment of CML and is increasingly used in the stem cell transplantation (SCT) setting. Since ABL-dependent intracellular signaling molecules are involved in T-cell activation, imatinib may affect T-cell responses in vivo, thus affecting T-cell function in CML patients, disrupting immune reconstitution after allogeneic SCT and/or impeding the graft-versus-leukemia effect. Here we demonstrate that imatinib inhibits PHA-induced proliferation of normal peripheral blood mononuclear cells at in vitro concentrations (1-5 micromol/l) representative of the pharmacological doses used therapeutically in vivo. The effect is not dependent on antigen-presenting cells because CD3/CD28-induced T-cell stimulation was similarly inhibited by imatinib. Dose-dependent inhibition of the proliferative response of purified CD8+ and CD4+ T lymphocytes to anti-CD3/CD28 was similarly observed and associated with reduction in IFN-gamma production. The inhibitory effect could not be ascribed to an increased rate of apoptosis but the expression of activation markers on CD3+ T cells was significantly reduced in the presence of imatinib (1-5 micromol/L). Inhibition of T-cell proliferation was reversible after removal of the drug from the cultures. Thus, imatinib inhibits T-cell proliferation in vitro, an effect that is APC-independent, reversible, and does not involve apoptosis induction.

Benzamides↗

PubMed2004

Time/duration effectiveness of sildenafil versus tadalafil in the treatment of erectile dysfunction in male spinal cord-injured patients.

STUDY DESIGN: A randomized, blinded, crossover clinical trial comparing sildenafil versus tadalafil for erectile dysfunction (ED) in male spinal cord-injured (SCI) patients. OBJECTIVES: To compare the safety, time/duration effectiveness, and the impact on the quality of life (QoL) of tadalafil 10 mg versus sildenafil 50 mg. SETTING: Neurourology Section, Careggi Hospital, Florence, Italy. METHODS: During a screening (visit 1), a diary card was distributed, in which the subjects assessed, after each attempt at intercourse the quality of their erection, responding (Yes/No) to both Sexual Encounter Profile Questions 2 (SEP2) and 3 (SEP3). The subjects made at least four attempts at intercourse. At visit 2, 15 patients (group 1) were assigned sildenafil and 15 (group 2) started with tadalafil. Responses to baseline International Index of Erectile Function 5 items (IIEF-5), Questions 13-14 (IIEF 15 items) and SEP diary were recorded. Patients attempted intercourse on four separate occasions: within 4 h of taking the first tablet, within 12 h for the second tablet, 24 h for the third, and the fourth from 24 to 36 h. At visit 3, the investigators evaluated the effectiveness with the same measures used at baseline. After a wash-out period, at visit 4, Group 1 was given tadalafil, and Group 2 was given sildenafil. Patients were required to observe the same criteria in taking the four tablets as in visit 2. After 4 weeks (visit 5), we evaluated the patients as we did in visit 3. RESULTS: Overall, 28 patients completed the study. No subjects discontinued the drugs due to drawbacks. Tadalafil allowed a majority of men in this trial to achieve both normal sexual functioning up to 24 h postdosing compared to sildenafil (P<0.01) and improved overall sex life satisfaction as well as sexual relations with partner. CONCLUSION: Based on these data, tadalafil may have the potential to become an important treatment option for ED in SCI patients. SPONSORSHIP: This study was not sponsored.

Carbolines↗

PubMed2004

Genetic alterations in hereditary breast cancer.

Genetic linkage studies have led to the identification of highly penetrant genes as the possible cause of inherited cancer risk in many cancer-prone families. Most women with a family history of breast/ovarian cancer have tumors characterized by alterations in particular genes, mainly BRCA1 and BRCA2, but also CHK2, ATM, STK11 and others. This paper examines the BRCA1 and BRCA2 genes, focusing on the Italian pattern of mutations. The function of these two genes, classified as tumor suppressors, is linked with key metabolic mechanisms such as DNA damage repair, regulation of gene expression and cell cycle control. The pathological BRCA allelic variants may cause alteration of protein function, transcriptional activity and DNA repair; accumulation of the defects leads to widespread chromosome instability that may be directly responsible for cancer formation. In fact, mutations in BRCA1 and BRCA2, conferring a highly increased susceptibility to breast and ovarian cancer, do not lead to cancer by themselves. The current consensus is that these are 'caretaker' genes, which, when inactivated, allow other genetic defects to accumulate. The nature of these other molecular events may define the pathway through which BRCA1 and BRCA2 act. The BRCA mutation spectrum is complex, and the significance of most nucleotide alterations is difficult to understand. Moreover, the mutation pattern seems to be related to ethnicity. The Italian Consortium of Hereditary Breast and Ovarian Cancer has reviewed 1758 families; 23% have been found to be carriers of pathogenetic mutations in BRCA1 or BRCA2. Founder mutations have been described in geographically restricted areas of Italy; a regional founder effect has been demonstrated in Italy for the mutations BRCA1 5083del19 and BRCA2 8765delAG, and a probable new founder mutation has been characterized in Tuscany. The presence of founder mutations has practical implications for genetic testing.

Adult↗

PubMed2004

Differential expression of CTLA-4 among T cell subsets.

CTLA-4 (CD152), the CD28 homologue, is a costimulatory molecule with negative effects on T cell activation. In addition to its role in the termination of activation, CTLA-4 has been implicated in anergy induction and the function of regulatory cells. As an intracellular molecule, it must first relocate to the cell surface and be ligated, in order to inhibit activation. Although some studies have investigated CTLA-4 expression on CD4(+) T cells, evidence is lacking regarding the kinetics of expression, and expression on T cell subpopulations. We have investigated CTLA-4 kinetics on human purified peripheral CD4(+), naïve, memory, CD4(+)CD25(-), CD4(+)CD25(+) regulatory T cells, and T cell clones. Intracellular stores of CTLA-4 were shown to be very low in naïve T cells, whilst significant amounts were present in memory T cells and T cell clones. Cell surface CTLA-4 expression was then investigated on CD4(+)CD45RA(+) (naïve), CD4(+)CD45RO(+) (memory), CD4(+)CD25(-), and CD4(+)CD25(+) T cells. CD25 and CD45RO are both expressed by regulatory T cells. On naïve and CD4(+)CD25(-) T cells, CTLA-4 expression declined after four hours. In contrast, on memory and CD4(+)CD25(+) T cells, high levels of expression were maintained until at least 48 hours. In addition, significant CTLA-4 expression was observed on T cell clones following anergy induction, indicating the potential involvement of CTLA-4 also in this form of tolerance.

Antigens, CD↗