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The MGTX trial provided evidence that, in general, thymectomy is beneficial in adult patients up to 60 years of age with anti-acetylcholine receptor-positive, nonthymomatous myasthenia gravis (MG). This finding supports the long-held view that the pathogenesis of this type of MG (early-onset MG (EOMG)) starts inside the thymus, results in the long-term intrathymic recruitment of autoantibody-producing B cells and plasma cells, and eventually spreads to the peripheral immune system. However, observed clinical responses to treatment in the MGTX trial were diverse. This might be due to heterogeneous epidemiological and genetic features of EOMG patients and variable durations of corticosteroid treatment before surgery, including a paucity of patients that were corticosteroid naive. Furthermore, the observed histological heterogeneity suggests that a single pathogenetic model may not fully reflect the spectrum of events that modify the course of EOMG. Here, we describe the morphology of the normal and MG-associated thymus, how to evaluate morphological changes, and the current pathogenetic model of EOMG and discuss how it could be refined by integrating MGTX-derived histological findings in thymectomy specimens and associated clinical observations.

According to the 2014 Japanese clinical guidelines for myasthenia gravis, the most important priority in treatment is maintaining patients' health-related quality of life. Therefore, the initial treatment goal is defined as maintaining a postintervention status of minimal manifestations or better (according to the Myasthenia Gravis Foundation of America classification) with an oral prednisolone dose of 5 mg/day or less. Every effort should be made to attain this level as rapidly as possible. To achieve this goal, the guidelines recommend minimizing the oral prednisolone dose, starting calcineurin inhibitors early in the course of treatment, using intravenous methylprednisolone infusion judiciously (often combined with plasma exchange/plasmapheresis or intravenous immunoglobulin), and effectively treating patients with an early, fast-acting treatment strategy. The early, fast-acting treatment strategy enables more frequent and earlier attainment of the initial goal than other strategies. Thymectomy is considered an option for treating nonthymomatous early-onset myasthenia gravis in patients with antiacetylcholine receptor antibodies and thymic hyperplasia in the early stages of the disease.

A task force of the Myasthenia Gravis Foundation of America recently published a formal consensus statement intended to be a treatment guide for clinicians caring for myasthenia gravis (MG) patients worldwide. Its development was stimulated by the fact that there is generally no accepted standard of care for MG, and no one treatment is best for all MG patients. Also, there are few randomized trials of treatments in current use, and the generalizability of the few trials that have been successful may be difficult. Fifteen international experts in MG participated in the consensus process, which used a simple consensus to develop preliminary definitions and the RAND/UCLA Appropriateness Method to quantify agreement on treatment guidance statements for seven topics: symptomatic and immunosuppressive treatment, intravenous immunoglobulin and plasma exchange, impending and manifest myasthenic crisis, thymectomy, juvenile MG, MG with muscle-specific tyrosine kinase antibodies, and MG in pregnancy. The executive summary of the guidance statement was published with open access to facilitate access by patients and healthcare professionals, and the full statement, with extensive background information, is available online. The guidance statement is a living document that will require updates as new treatments and new information on current treatments become available.

MicroRNAs (miRNAs) are small noncoding RNA molecules that bind to specific mRNA targets and regulate a wide range of important biological processes within cells. Circulating miRNAs are released into the extracellular space and can be measured in most biofluids, including blood serum and plasma. Recently, circulating miRNAs have emerged as easily accessible markers in various body fluids with different profiles and quantities specific for different human disorders, including autoimmune diseases. In myasthenia gravis (MG), diagnostic tests such as titers of serum autoantibodies specific for either the acetylcholine receptor (AChR+ ) or muscle-specific tyrosine kinase (MuSK+ ) do not necessarily reflect disease progression, and there is a great need for reliable objective biomarkers to monitor the disease course and therapeutic response. Recent studies in AChR+ MG revealed elevated levels of the immuno-miRNAs miR-150-5p and miR-21-5p. Of particular importance, levels of miR-150-5p were lower in immunosuppressed patients and in patients with clinical improvement following thymectomy. In MuSK+ MG, another profile of circulating miRNAs was found, including upregulation of the let-7 family of miRNAs. Here, we summarize the potential role of circulating miRNAs as biomarkers in general and in MG, and highlight important considerations for the analysis of circulating miRNA.

A task force of the Myasthenia Gravis Foundation of America recently published a formal consensus statement intended to be a treatment guide for clinicians caring for myasthenia gravis (MG) patients worldwide. Its development was stimulated by the fact that there is generally no accepted standard of care for MG, and no one treatment is best for all MG patients. Also, there are few randomized trials of treatments in current use, and the generalizability of the few trials that have been successful may be difficult. Fifteen international experts in MG participated in the consensus process, which used a simple consensus to develop preliminary definitions and the RAND/UCLA Appropriateness Method to quantify agreement on treatment guidance statements for seven topics: symptomatic and immunosuppressive treatment, intravenous immunoglobulin and plasma exchange, impending and manifest myasthenic crisis, thymectomy, juvenile MG, MG with muscle-specific tyrosine kinase antibodies, and MG in pregnancy. The executive summary of the guidance statement was published with open access to facilitate access by patients and healthcare professionals, and the full statement, with extensive background information, is available online. The guidance statement is a living document that will require updates as new treatments and new information on current treatments become available.

According to the 2014 Japanese clinical guidelines for myasthenia gravis, the most important priority in treatment is maintaining patients' health-related quality of life. Therefore, the initial treatment goal is defined as maintaining a postintervention status of minimal manifestations or better (according to the Myasthenia Gravis Foundation of America classification) with an oral prednisolone dose of 5 mg/day or less. Every effort should be made to attain this level as rapidly as possible. To achieve this goal, the guidelines recommend minimizing the oral prednisolone dose, starting calcineurin inhibitors early in the course of treatment, using intravenous methylprednisolone infusion judiciously (often combined with plasma exchange/plasmapheresis or intravenous immunoglobulin), and effectively treating patients with an early, fast-acting treatment strategy. The early, fast-acting treatment strategy enables more frequent and earlier attainment of the initial goal than other strategies. Thymectomy is considered an option for treating nonthymomatous early-onset myasthenia gravis in patients with antiacetylcholine receptor antibodies and thymic hyperplasia in the early stages of the disease.

The MGTX trial provided evidence that, in general, thymectomy is beneficial in adult patients up to 60 years of age with anti-acetylcholine receptor-positive, nonthymomatous myasthenia gravis (MG). This finding supports the long-held view that the pathogenesis of this type of MG (early-onset MG (EOMG)) starts inside the thymus, results in the long-term intrathymic recruitment of autoantibody-producing B cells and plasma cells, and eventually spreads to the peripheral immune system. However, observed clinical responses to treatment in the MGTX trial were diverse. This might be due to heterogeneous epidemiological and genetic features of EOMG patients and variable durations of corticosteroid treatment before surgery, including a paucity of patients that were corticosteroid naive. Furthermore, the observed histological heterogeneity suggests that a single pathogenetic model may not fully reflect the spectrum of events that modify the course of EOMG. Here, we describe the morphology of the normal and MG-associated thymus, how to evaluate morphological changes, and the current pathogenetic model of EOMG and discuss how it could be refined by integrating MGTX-derived histological findings in thymectomy specimens and associated clinical observations.

The MGTX trial is the first prospective, randomized clinical trial that aims to evaluate the impact of extended transsternal thymectomy on myasthenic symptoms, prednisone requirements, and quality of life in patients with nonthymomatous, anti-acetylcholine receptor autoantibody-positive myasthenia gravis (MG). Here, we give an overview of the rationale of thymectomy and the standardized macroscopic and histopathological work-up of thymectomy specimens as fixed in MGTX standard operating procedures, including the grading of thymic lymphofollicular hyperplasia and the morphometric strategy to assess thymic involution.

The primary study [MGTX] aims to answer three questions: does extended transsternal thymectomy combined with the prednisone protocol, when compared with the prednisone protocol alone: (1) result in a greater improvement in myasthenic weakness, (2) result in a lower total dose of prednisone, thus decreasing the likelihood of concurrent and long-term toxic effects, (3) enhance the quality of life by reducing adverse events and symptoms associated with the therapies? Inclusion criteria are MGFA Class 2, 3, or 4; acetylcholine receptor antibody positive; age at least 18.0 years and

There continues to be debate concerning which thymectomy technique is the procedure of choice in the treatment of nonthymomatous myasthenia gravis (MG). The debate persists primarily because of the lack of controlled prospective studies but also because of the varying presentations and clinical courses of MG patients. Analysis has been complicated by the absence, until very recently, of accepted objective definitions of severity of the illness and response to therapy as well as variable patient selection, timing of surgery, type of surgery, and methods of analysis of results. Without resolution of these issues by properly designed prospective studies, there can be no unequivocally valid comparison of the various thymectomy techniques. In this review, attempts have been made to clarify some of the controversial issues concerning the selection of a thymectomy technique in the treatment of nonthymomatous MG and to make limited recommendations based on the best available evidence.

Although once an often fatal illness, myasthenia gravis can now be well managed with relatively safe and effective therapies. Prior to 1960 mortality for myasthenia gravis was approximately 30%. In the current era, mortality should be less than 5%. Major therapeutic advances by decade were: physostigmine and thymectomy (1930s); mechanical ventilation (1950s); corticosteroids and plasmapheresis (1960s); azathioprine (1960s-1970s); cyclosporine (1980s); intravenous gamma globulins (1980s-1990s); and most recently mycophenolate mofetil (1990s-2000s). Modern management involves a graded approach, beginning with cholinesterase inhibitors for mild symptoms and advancing to immunomodulating medications for more severe weakness. We now have several immunomodulating agents from which to choose: selection is based largely on time to clinical effect and adverse effects. The various available treatment modalities all have their limitations. In addition, some controversies remain regarding the effectiveness of some of the commonly used myasthenia gravis treatments. Recently completed and ongoing clinical trials suggest that there is still equipoise regarding the benefit of mycophenolate mofetil and thymectomy. Hopefully, the future will be promising, with clinical trials involving novel immunotherapeutic strategies.

Complete thymectomy (Thx) is a crucial part of treatment for myasthenia gravis (MG) and thymoma. The discussion about the necessity of radical, complete Thx and reduced invasiveness has led to no less than 14 different surgical approaches for Thx. The latest development is robotic-assisted surgery. Though its impact on minimally invasive surgery is not yet clear, it seems to be most promising for surgery in remote, narrow anatomical regions like the mediastinum. One hundred six consecutive robotic-assisted thymectomies (rThx) with the da Vinci robotic surgical system were performed between January 2003 and April 2007 in a prospective single-center study. Postoperative morbidity was recorded according to the Myasthenia Gravis Foundation of America (MGFA) classification. With zero mortality, the overall postoperative morbidity rate was 2%. The cumulative complete stable remission rate of MG was > 40% for all patients, and there was no statistical difference as compared to non-thymomatous MG patients. The cumulative rate of minimal manifestations (MM0-MM3) according to the MGFA classification showed a postoperative improvement in quality of life for most of the patients. The da Vinci robotic system allowed for technical refinements of the well-defined operation technique of thoracoscopic Thx (tThx). From the technical point of view, rThx has advantages for mediastinal dissection. rThx had a shorter learning curve. There might be better outcome results for rThx in MG patients, as compared with nonrobotic tThx. Therefore, rThx is a promising technique for minimally invasive Thx.

A small but important proportion of patients with myasthenia gravis (MG) are refractory to conventional immunotherapy. We have treated 12 such patients by "rebooting" the immune system with high-dose cyclophosphamide (Hi Cy, 200 mg/kg), which largely eliminates the mature immune system, while leaving hematopoietic precursors intact. The objective of this report is to describe the clinical and immunologic results of Hi Cy treatment of refractory MG. We have followed 12 patients clinically for 1-9 years, and have analyzed their humoral and cellular immunologic parameters. Hi Cy is safe and effective. All but one of the patients experienced dramatic clinical improvement for variable periods from 5 months to 7.5 years, lasting for more than 1 year in seven of the patients. Two patients are still in treatment-free remission at 5.5 and 7.5 years, and five have achieved responsiveness to immunosuppressive agents that were previously ineffective. Hi Cy typically reduced, but did not completely eliminate, antibodies to the autoantigen AChR or to tetanus or diphtheria toxin; re-immunization with tetanus or diphtheria toxoid increased the antibody levels. Despite prior thymectomy, T cell receptor excision circles, generally considered to reflect thymic emigrant T cells, were produced by all patients. Hi Cy treatment results in effective, but often not permanent, remission in most refractory myasthenic patients, suggesting that the immune system is in fact "rebooted," but not "reformatted." We therefore recommend that treatment of refractory MG with Hi Cy be followed with maintenance immunotherapy.

The ideal operative technique for thymectomy in myasthenia gravis remains controversial. Most surgeons perform thymectomy via median sternotomy, some supplementing this with an even more extensive mediastinal and cervical dissection designed to remove all areas of possible ectopic thymic tissue. We and others have advocated a transcervical approach that is less morbid and costly than sternotomy approaches. The transcervical approach allows a complete extracapsular thymic resection, but it does not address all areas of potential ectopic thymic tissue. We have published our experience with 151 extended transcervical thymectomies (TCT). At mean follow-up of 53 months (complete follow-up in 97%), Kaplan-Meier estimates of complete stable remission were 33% and 35% at 3 and 6 years. If one includes patients who became asymptomatic but remained on low dose, single-drug immunosuppression as complete remissions (CRs), then the CR rates were 43% and 45% at 3 and 6 years. Longer term (mean 83 months) follow-up of the earliest 84 patients in the series showed preserved CR rates. On multivariate analysis, only preoperative Osserman Class (group mean 2.3) was significantly associated with improved CR rate. These results were obtained with a major operative complication rate of 0.7% and minor complication rate of 6.6%, and nearly every operation was performed without the need for overnight hospital admission. We believe that these response rates following TCT are sufficiently similar to those following transsternal techniques of thymectomy to allow us to recommend this less morbid and less costly operation as an eminently reasonable choice in the surgical treatment of myasthenia gravis.

Tacrolimus is a macrolide T cell immunomodulator that is used in myasthenia gravis (MG) patients to affect muscle contraction (ryanodine receptor by modulating intracellular calcium-release channels and increasing muscular strength), glucocorticoid receptors (increasing intracellular concentration of steroids and blocking the steroid export mechanism), and an increase in T cell apoptosis. In this study, we report the results of low-dose tacrolimus (0.1 mg/kg/day) treatment in 212 MG patients. There were 110 thymectomized, cyclosporine- and prednisone-dependent patients; 68 thymectomized patients who started tacrolimus early postoperatively (24 h after operation); and 34 patients over 60 years old with nonthymomatous generalized MG or in whom thymectomy was contraindicated. The mean follow-up time was 49.3 +/- 18.1 months. Muscular strength showed an increase of 23% after 1 month of treatment and 29% at the end of the study. The acetylcholine receptor antibodies decreased significantly from a mean of 33.5 nmol/L at base line to 7.8 nmol/L at the final visit. In the thymectomy group with combined prednisone and tacrolimus stratified by histology of the thymus, the mean probability to attain complete stable remission at 5 years was 80.8% in patients with hyperplasia, 48.1% in thymic involution, and 9.3% in patients with thymoma. In 4.9% of patients, tacrolimus was withdrawn because of major adverse effects. Our results suggest that a low dose of tacrolimus is effective for MG and could be included to the armamentarium for this autoimmune disease. The present results should be interpreted considering the limitations of a retrospective clinical study. Confirmation of these results in randomized studies is desirable.

We have defined myasthenia gravis (MG) in the elderly as onset after the age of 50 years. MG is diagnosed more often today than previously. The increase is mainly found in patients over the age of 50 years. Neurologists therefore see more old patients with MG now than before. Prevalence of the early-onset form of MG seems to be unchanged. Recent data indicate that MG may still be substantially underdiagnosed in very old people. Ptosis, diplopia, weakness of the facial muscles, and problems of articulation are important clinical signs in MG and are easier to detect in a youthful appearance. Since ageing causes a decrease in the total eyelid area with sagging of the lower eyelids, a ptosis may be more difficult to diagnose in the elderly. In addition, diplopia may not be detected because of reduced vision due to macular degeneration or cataract formation. Ocular symptoms of MG are therefore more easily missed in the elderly. Thymomatous MG is more common among older patients than it is in younger onset. The mean age at onset of MG for thymoma cases is 50-60 years. Approximately 10-15% of all MG patients have a thymoma, and around 40% of all thymoma cases are associated with MG. During normal aging, the thymus tissue becomes atrophic and replaced with fat. Recent data on MG thymus pathology suggest that lymphocyte accumulation indicating residual thymus may also be found in the elderly, and that there is little qualitative difference between the young and the old thymus from MG patients. The mean concentration of antibodies to acetylcholine receptor (AChR) is lower in MG in the elderly than in early-onset or thymoma-associated MG. Seronegative MG is less common among older patients. Approximately 30% of patients with late-onset, nonthymoma MG have antibodies to titin, while such antibodies are extremely scarce in early-onset MG. Titin antibodies in MG patients seem to be associated with a higher frequency of DR7 antigen and a decrease of DR3 antigen. The antibody response in MG may therefore be influenced by the genetic background.

Thymectomy has been regularly used in the management of nonthymomatous autoimmune myasthenia gravis (MG), but its benefits have not been established in a randomized, controlled trial. The widespread use of thymectomy in MG patients without thymoma is largely based on retrospective, nonrandomized case series that have produced a consensus that the procedure is sometimes beneficial. Still, the benefits and utilization of thymectomy are actively debated among MG experts. In this paper, we describe the development of a multicenter, international trial to determine whether extended transsternal thymectomy reduces corticosteroid requirements for patients with generalized AChR antibody-positive nonthymomatous MG.

Data from 756 myasthenic patients were analyzed for diagnostic criteria, clinical aspects, and therapeutic approaches. The patients were followed up at our institution from 1981 to 2001. Clinical evaluation was performed according to the myasthenia gravis score adopted at our clinic. Clinical features of each patient (comprising demographic, clinical, neurophysiological, immunological, radiological, and surgical data, as well as serial myasthenia gravis scores) were filed in a relational database containing more than 7000 records. Clinical efficacy and variables influencing outcome were assessed by life-table methods and Cox proportional hazards regression analysis. Complete stable remission, as defined by the Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America, was the end point for good prognosis. Four hundred and ninety-nine patients (66%) were female and 257 (34%) were male. Mean follow-up was 55.1 +/- 48.1 months. Onset of symptoms peaked in the third decade in females, whereas the male distribution was bimodal with peaks in the third and sixth decades. Modality of myasthenia gravis presentation was as follows: ocular, 39.3%; generalized, 28.5%; bulbar, 31.3%; and respiratory, 0.8%. Thymectomy was carried out on 63.7% of our patients by different approaches: (1) transcervical; (2) transsternal; (3) video-thoracoscopic mini-invasive surgery. The last approach has been preferentially used in more recent years and accounted for 62.4% of the thymectomized myasthenia gravis population. Univariate analysis and Kaplan-Meier analysis showed that variables such as sex (female), age at onset (below 40 years), thymectomy, and histological diagnosis of thymic hyperplasia were significantly associated with complete stable remission, whereas on multivariate analysis only age at onset below 40 years and thymectomy were confirmed.

Mice are protected from experimental autoimmune encephalomyelitis (EAE) when fed myelin basic protein (MBP). Thymectomized mice do not exhibit oral tolerance. We found evidence for two mechanisms to explain the role of the thymus in oral tolerance: a site for deletion of autoreactive T cells and a source of regulatory T cells.

Objective: To identify the response to thymectomy and the factors associated with a poor response, a nested case-control study was performed on 132 patients with an established diag

There continues to be debate concerning which thymectomy technique is the procedure of choice in the treatment of nonthymomatous myasthenia gravis (MG). The debate persists primarily because of the lack of controlled prospective studies but also because of the varying presentations and clinical courses of MG patients. Analysis has been complicated by the absence, until very recently, of accepted objective definitions of severity of the illness and response to therapy as well as variable patient selection, timing of surgery, type of surgery, and methods of analysis of results. Without resolution of these issues by properly designed prospective studies, there can be no unequivocally valid comparison of the various thymectomy techniques. In this review, attempts have been made to clarify some of the controversial issues concerning the selection of a thymectomy technique in the treatment of nonthymomatous MG and to make limited recommendations based on the best available evidence.

Tacrolimus is a macrolide T cell immunomodulator that is used in myasthenia gravis (MG) patients to affect muscle contraction (ryanodine receptor by modulating intracellular calcium-release channels and increasing muscular strength), glucocorticoid receptors (increasing intracellular concentration of steroids and blocking the steroid export mechanism), and an increase in T cell apoptosis. In this study, we report the results of low-dose tacrolimus (0.1 mg/kg/day) treatment in 212 MG patients. There were 110 thymectomized, cyclosporine- and prednisone-dependent patients; 68 thymectomized patients who started tacrolimus early postoperatively (24 h after operation); and 34 patients over 60 years old with nonthymomatous generalized MG or in whom thymectomy was contraindicated. The mean follow-up time was 49.3 +/- 18.1 months. Muscular strength showed an increase of 23% after 1 month of treatment and 29% at the end of the study. The acetylcholine receptor antibodies decreased significantly from a mean of 33.5 nmol/L at base line to 7.8 nmol/L at the final visit. In the thymectomy group with combined prednisone and tacrolimus stratified by histology of the thymus, the mean probability to attain complete stable remission at 5 years was 80.8% in patients with hyperplasia, 48.1% in thymic involution, and 9.3% in patients with thymoma. In 4.9% of patients, tacrolimus was withdrawn because of major adverse effects. Our results suggest that a low dose of tacrolimus is effective for MG and could be included to the armamentarium for this autoimmune disease. The present results should be interpreted considering the limitations of a retrospective clinical study. Confirmation of these results in randomized studies is desirable.

From a historical perspective, the studies that led to the isolation and characterization of the thymosins began in earnest in the early 1960s in the laboratory of Abraham White at the Albert Einstein College of Medicine in New York. In a 1966 paper in the Proceedings of the National Academy of Sciences, U.S., we first named these thymic-derived factors "Thymosins." By 1972, the thymosin team had moved to the University of Texas Medical Branch in Galveston (UTMB) where an extremely talented group of young scientists and students succeeded over the next 6 years in preparing and testing a highly active partially purified calf thymus preparation, termed thymosin fraction-5 (TF5), which was amenable for scale-up and suitable for clinical use. In 1974, we received the first IND for a thymic hormone preparation from the FDA to begin a phase-I study with TF5 in children with primary immunodeficiency diseases at the University of California Medical Center in San Francisco. The immunorestorative and potentially life-saving properties of TF5 in clinical medicine were first documented in a landmark paper in 1975 by Drs. Arthur Ammann and Diane Wara in the New England Journal of Medicine. TF5 consists of a family of at least 40 mostly small acidic polypeptides, with molecular weights ranging from 1000 to 15,000 Da. This article will identify the key scientists and the milestones involved in the initial studies with TF5 that have led to the chemical characterization of the thymosins and to translational studies from the lab bench to the clinic.

The pathogenesis of myasthenia gravis (MG) involves a T cell-directed antibody-mediated autoimmune attack on the nicotinic acetylcholine receptor (AChR) or, occasionally, on other postsynaptic antigens. The antibodies induce their effects through complement-mediated destruction of the postsynaptic endplate membrane with resultant reduction in endplate AChR, and to a lesser degree by increased turnover of endplate AChR or blockade of AChR function. Considerable progress in the treatment of MG has accrued from so-called symptomatic treatments, including improved critical care of seriously ill patients and medications (e.g., cholinesterase inhibitors) increasing the concentration of acetylcholine at the remaining endplate AChRs. Information from other autoimmune diseases and from the response of the normal immune system to invading pathogens supports the view that the course of MG is characterized by exacerbations and remissions. Therefore, the goal in MG treatment is to induce and maintain a remission. This usually involves combinations of short-term and long-term immunosuppressive agents. Selection of the particular combinations of agents in a given patient is guided by the goal of minimizing the cost/benefit ratio of the regimen in an individual patient. In general, the plan involves an initial forceful attack followed by a slow and measured withdrawal.

The present study is aimed at exploring the regulatory CD4(+)CD25(+) T cells in the thymus from myasthenia gravis (MG) patients. In early-onset MG, the thymus is hyperplastic and contains autoreactive activated T cells. Preliminary studies indicate that these CD4(+)CD25(+) cells include activated autoreactive T cells. Studies to characterize the phenotype and suppressive capacity of these cells will be discussed.

Thymectomized calves were selectively depleted of CD4+ T lymphocytes with a monoclonal antibody (mAb) specific for the bovine CD4 monomer (ILA-11). Calves were treated with high loading doses of ILA-11 during the first week of the study then treated with subsequent lower maintenance doses. Depletion of CD4+ T lymphocytes was assessed weekly by flow cytometric analysis of PBMC and mononuclear cells from lymph node and spleen biopsies. Treatment with high doses of ILA-11 resulted in rapid and marked depletion of CD4+ T lymphocytes from the peripheral blood, peripheral lymph nodes, and spleen. Although CD4+ T lymphocytes slowly returned to the peripheral blood, peripheral lymph nodes, and spleen by day 21 post-treatment, the numbers of CD4+ T lymphocytes in depleted calves remained below pre-depletion levels for the duration of the study. CD4+ T lymphocytes failed to be effectively depleted from a non-thymectomized calf treated with the mAb ILA-11. Development of a T lymphocyte depletion model in thymectomized calves will permit testing of the hypothesis that CD4+ T lymphocytes and IFN-gamma are required in cattle for control of acute anaplasmosis. In subsequent planned studies, thymectomized calves depleted of CD4+ T lymphocytes will be experimentally infected with A. marginale and parameters of disease compared between depleted and non-depleted calves.