Vaccination in post-tuberculosis lung disease management: A review of the evidence.

INTRODUCTION AND OBJECTIVES: Post-tuberculosis lung disease (PTLD), as other chronic respiratory disorders, may have infectious complications; some of them can be prevented with vaccinations. So far, no document has discussed the potential role of vaccination in PTLD. Therefore, the objective of this review was to describe vaccination recommendations to prevent infections potentially capable of complicating PTLD. MATERIALS AND METHODS: A non-systematic review of the literature was conducted. The following keywords were used: tuberculosis, vaccination, vaccines and PTLD. PubMed/MEDLINE and Embase were used as the search engine, focusing on English-language literature only. RESULTS: We identified 9 vaccines potentially useful in PTLD. Influenza, pneumococcal and anti-COVID-19 vaccinations should be recommended. Patients with PTLD can also benefit from vaccination against shingles. Vaccination against pertussis is mainly relevant during childhood. Diphtheria, tetanus and measles vaccination are recommended for general population and should be considered in patients with PTLD not previously vaccinated. Tdap (Tetanus, diphtheria, and pertussis) booster should be repeated in every adult every ten years. Vaccination against BCG retains its importance during early childhood in countries where TB is endemic. CONCLUSIONS: Vaccination deserves to be considered among the strategies to prevent and/or mitigate PTLD complications. Further evidence is necessary to better understand which vaccines have the greatest impact and cost-benefit.

Spondylodiscitis: is really all well defined?

The term spondylodiscitis describes the infection of both the intervertebral disc space and the adjacent vertebrae. Pyogenic Vertebral Osteomyelitis (PVO) is more common in older patients (mean age 59-69 years) with a male preponderance (52-69%). Recent studies reported an alarming increase of incidence over the last 20 years, due to the increase of diagnostic sensibility, the increase of the average lifetime and to the consequent association of chronic disabling pathologies, of immunosuppression, of surgical or invasive procedure. Improvements in radiological diagnosis, surgical techniques, and management of antimicrobial therapy have greatly improved PVO clinical outcome, but morbidity remains significant mostly because of the delay of diagnosis. The non-specific features of this infection can lead to underestimate the patient conditions, ending to a significant delay in diagnosis, reported from 30 to 90 days, and consequently to severe impairments, such as spine deformity and permanent neurological deficit. The duration of medical treatment is not yet established, and further randomized trials are needed to define it.

Prostate Cancer in Renal Transplant Recipients: Diagnosis and Treatment.

BACKGROUND: We currently know that prostate cancer (Pca) risk is reduced in patients undergoing kidney transplantation. However, its impact and treatment are not widely studied. METHODS: This was a retrospective study of male patients submitted to kidney transplantation in our center from 1980 to 2016 evaluating incidence, treatment, and follow-up of Pca in our population. RESULTS: In 1805 patients undergoing kidney transplantation, 20 men were diagnosed with Pca, leading to an incidence of 1.1%. Median age at renal transplantation was 53.4 years with a median age at diagnosis of Pca of 61.2 years. Initial median prostate-specific antigen (PSA) was 6 ng/mL and Gleason score was 7 (3 + 4) in about 50% of cases. Bone metastasis developed in 10% and no visceral metastases were diagnosed. The majority of patients were submitted to radical prostatectomy and bilateral pelvic lymph node dissection. Some other cancers occurred in these patients such as skin and pulmonary cancers. In 35% of the cases, the graft was lost. The main cause of patient death was cardiovascular. The mean graft survival was about 14 years. The majority of patients are alive with functioning grafts (65%). CONCLUSION: In our center the clinical incidence of Pca in patients undergoing kidney transplantation is 1.1% and surgical treatment seems to be a good initial option.

Dynamical Two-Mode Squeezing of Thermal Fluctuations in a Cavity Optomechanical System.

We report the experimental observation of two-mode squeezing in the oscillation quadratures of a thermal micro-oscillator. This effect is obtained by parametric modulation of the optical spring in a cavity optomechanical system. In addition to stationary variance measurements, we describe the dynamic behavior in the regime of pulsed parametric excitation, showing an enhanced squeezing effect surpassing the stationary 3 dB limit. While the present experiment is in the classical regime, our technique can be exploited to produce entangled, macroscopic quantum optomechanical modes.

Approaching Free Fall on Two Degrees of Freedom: Simultaneous Measurement of Residual Force and Torque on a Double Torsion Pendulum.

A torsion pendulum with 2 soft degrees of freedom (DOFs), realized by off-axis cascading two torsion fibers, has been built and operated. This instrument helps characterize the geodesic motion of a test mass for LISA Pathfinder or any other free-fall space mission, providing information on cross talk and other effects that cannot be detected when monitoring a single DOF. We show that it is possible to simultaneously measure both the residual force and the residual torque acting on a quasifree test mass. As an example of the investigations that a double pendulum allows, we report the measurement of the force-to-torque cross talk, i.e., the amount of actuation signal, produced by applying a force on the suspended test mass, that leaks into the rotational DOF, detected by measuring the corresponding (unwanted) torque.

Small kidneys for large recipients: does size matter in renal transplantation?

BACKGROUND: Imbalance between transplanted renal mass and the metabolic demands of the recipient has been identified as a predictor of renal graft function. Multiple factors have been used to test this influence, but none of them is consensually accepted. The aim of this study is to evaluate the influence of the imbalance between transplanted renal mass and the metabolic needs of the recipient by analyzing the relationship between the ratio of the weight of the renal graft and the body weight of the recipient (Kw/Rw) on transplantation outcomes. METHODS: Prospective observational study of 236 first and single cadaveric renal transplants in non-hyperimmunized recipients was conducted. Grafts were orthogonally measured and weighed immediately before implantation, and these measures were correlated with donor and recipient data. According to the Kw/Rw ratio, patients were divided into three groups: Kw/Rw < 2.8 (P25), Kw/Rw = 2.8-4.2, and Kw/Rw > 4.2 (P75). After a mean follow-up of 5.2 years, transplant outcomes (delayed graft function; acute rejections; and estimated 1-, 6-, 12-, 36-, and 60-month renal function, graft, and patient survivals) were evaluated and correlated in uni- and multivariate analyses with the Kw/Rw ratio. RESULTS: Mean values for graft dimensions were 109.47 × 61.77 × 40.07 mm and the mean weight was 234.63 g. Mean calculated volume was 145.64 mL. The mean Kw/Rw ratio was 3.65 g/kg. These values were significantly lower for female grafts (3.91 vs 3.24, P < .001). According to the Kw/Rw ratio groups, there were no differences on delayed graft function, acute rejection episodes, and estimated graft function at the defined times. The increase in estimated glomerular filtration rate by a mean of 3.6 mL/min between 1 and 6 months for patients with Kw/Rw < 2.8 was not statistically relevant when compared to the higher ratio group with a mean variation of -0.91 mL/min (P = .222). Graft survival rate at 5 years after transplantation was 79% in the Kw/Rw < 2.8 group and 82% in the Kw/Rw > 4.2 group (P = .538). Patient survival rate at 5 years after transplantation was 85% in the Kw/Rw < 2.8 group and 92% in the high ratio group (P = .381). Kw/Rw ratio was not an independent risk factor for transplant failure at 5.2 years in a multivariate logistic regression analysis. Irrespective of recipient weight, graft survival was significantly higher for grafts with volume or weight above the 50 percentile (vol > 134 mL, P = .011 or weight > 226 g, P = .016). CONCLUSION: The imbalance between implanted renal mass and recipient metabolic demands does not seem to influence the functional outcomes and graft survival up to 60 months post-transplantation. Nevertheless, irrespective of recipient weight, graft survival is significantly higher for grafts with volume or weight above the 50 percentile.

Venous Thromboembolism in Cancer: Frequently Asked Questions When Guidelines are Inconclusive.

Management of Venous thromboembolism (VTE) in cancer patients is difficult when guidelines are inconclusive. To share a reasonable and homogeneous behavior in such circumstances, four issues, which are felt as problematic by oncologists and surgeons, have been selected; all were uncovered or only partially covered by current guidelines. Results from the literature and author's specific experience in the field were utilized to suggest reasonable solutions to the raised questions. The reported experience is the first to provide real-world management guidance for VTE in cancer patients. The effort of putting together literature review and author's experience brought to the adoption of a common behavior.

Kidney retransplantation: removal or persistence of the previous failed allograft?

A significant percentage of patients with failed renal graft are candidates for retransplantation. The outcomes of retransplantation are poorer than those of primary transplantation and sensitization is documented to be a major reason. The management of a failed allograft that is not immediately symptomatic is still very controversial. The aim of this study was to determine the impact of the failed allograft nephrectomy on a subsequent transplantation and its importance in the sensitization. We performed a retrospective analysis of the local prospective transplantation registry of the outcome of 126 second kidney transplantations among 2438 transplantations performed in our unit between June 1980 and March 2013, comparing those who underwent allograft nephrectomy prior to retransplantation with those who retained the failed graft. Primary endpoints were graft and patient survival. The levels of panel-reactive antibodies (PRA) and rate of acute rejections on retransplantation outcomes were also studied. Among the 126 patients who underwent a second renal transplantation, 76 (60.3%) had a prior graft nephrectomy (Group A), whereas 50 (39.7%) kept their failed graft (Group B). Group A showed significantly more positive PRA levels when compared with the other group (38% vs 10%; P < .001), as measured before the most recent transplantation, and a higher rate of acute rejection (19% vs 5.6%; P = .016). There were 28 (36%) renal allograft losses for Group A and 18 (36%) for those who had not had transplantectomy (P = not significant [NS]). One-, 3-, and 5-year graft survival rates were 96.6%, 90.7%, and 83.4%, respectively, in Group A and 95%, 82%, and 68.4%, respectively, in Group B, with no statistical differences (P = .19). Five-year actuarial patient survival rates in the 2 groups was 89.3% and 82.8%, respectively (P = .55). Multivariate analysis showed that PRA level and delayed graft function (DGF) had a statistically significant influence on graft survival (P = .028; odds ratio [OR] = 1.029; and P = .024; OR = 8.6), irrespective of whether the patient had graft nephrectomy or not. The allosensitization indicated by PRA increases after transplantectomy and leads to a higher incidence of acute rejection after retransplantation. Nephrectomy of failed allograft does not seem to significantly influence the survival of a subsequent graft. The decision to remove or retain a failed graft in the context of retransplantation should thus be based on known clinical indications for the procedure.

Renal transplantation with donors older than 70 years: does age matter?

PURPOSE: The need for organs for renal transplantation has encouraged the use of grafts from increasingly older donors. Studies of transplantation results with donors older than 70 years are sparse. The main purpose of this study is to compare the results of transplantation with donors older and younger than 70 years old. METHODS: This retrospective study included 1233 consecutive deceased-donor renal transplantations performed between January 1, 2001, and December 31, 2011. We compared outcomes of grafts from donors older than 70 years (group ≥ 70; n = 82) versus donors younger than 70 years (group < 70; n = 1151). RESULTS: Univariate analysis of pretransplantation data showed statistically significant differences (P < .05) among the following variables for the group < 70 and group ≥ 70, respectively: recipient age (46 ± 13 versus 61 ± 5 years), donor age (44 ± 16 versus 73 ± 3 years), donor male gender (69.4% versus 47.6%), use of antibody induction immunosuppression (51.7% versus 70.7%), and HLA compatibilities (2.4 versus 2). The group ≥ 70 showed increased postoperative minor complications: bleeding (8.5% versus 3.4%; P = .017), lymphocele formation (3.7% versus 0.5%; P = .011), and incisional hernia (2.4% versus 0.2%; P < .001). Regarding transplantation results, we observed that mean serum creatinine was significantly lower among group < 70, at 1, 3, 6, 12, 24, and 60 months after transplantation (P < .05). Cumulative graft survival at 1, 3, and 4 years was 90%, 85%, and 83% in the group < 70 versus 87%, 79%, and 72% in the group ≥ 70. In the subgroup of recipients younger than 60 years, we did not verify statistically significant differences in allograft survival between group ≥ 70 and group < 70. Using Cox regression for survival analysis, we verified that donor age was not an independent risk factor for graft failure. CONCLUSIONS: The group of patients who received kidneys from donors younger than 70 years achieved better transplantation outcomes. Nevertheless, kidneys from older donors represent an excellent alternative for older recipients.

Is incidentally detected pulmonary embolism in cancer patients less severe? A case-control study.

Incidental pulmonary embolism (PE) in cancer patients is usually thought to be of mild degree. We investigated the severity of PE and evaluated the potential of raising the suspicion of PE in such patients. The computed tomography (CT) extent of PE was evaluated in 19 consecutive unsuspected and 19 randomly selected symptomatic patients. A clinical pattern useful for suspecting PE was also searched. On CT, number of embolized vessels, location of emboli, and simple instrumental findings were not different in the two groups. PE is not less severe in unsuspected cancer patients; moreover, PE may be clinically suspected in such patients.

Donor cause of brain death in renal transplantation: a predictive factor for graft function?

PURPOSE: Our aim was to evaluate the influence of donor cause of brain death on the results of kidney transplantation. METHODS: This retrospective study included 896 consecutive deceased-donor renal transplantations performed between January 1, 2000, and December 31, 2009. We compared outcomes of grafts from donors after cerebrovascular accident (CVA; n = 371) versus head trauma (HT; n = 525). RESULTS: Univariate analysis of pretransplantation data showed statistically significant differences (P < .05): among the following variables for the HT versus CVA groups respectively: recipient age (43.63 ± 13.2 y vs 49.80 ± 12.5 y); donor age (36.06 ± 16.6 y vs 52.57 ± 13.2 y) and time on dialysis (50.67 ± 45.034 mo vs 59.39 ± 46.3 mo). Regarding transplantation results, we observed that mean serum creatinine was significantly lower among HT recipient, at 1, 3, 6, 12, and 24 months after transplantation (P < .05). Chronic allograft nephropathy (CAN) and delayed graft function were higher among the CVA group. HT group kidneys showed significantly longer mean survival times than CVA group kidneys (102.7 ± 3.9 mo vs 94.8 ± 5.6 mo; log rank: P = .04). Upon multivariate analysis donor cause of death was not identified as an independent risk factor for graft survival or occurrence of chronic allograft nephropathy. CONCLUSIONS: Transplantation results were better among the HT group. However multivariate regression analysis indicated that donor cause of death was not an independent risk factor for graft survival or occurrence of chronic allograft nephropathy.

The clinical course of pulmonary embolism patients anticoagulated for 1 year: results of a prospective, observational, cohort study.

BACKGROUND: Few studies have examined the clinical course of pulmonary embolism (PE) in patients anticoagulated continuously for 1 year. OBJECTIVE: We sought to determine the incidence of death, recurrent PE and bleeding during anticoagulation in the first year after acute PE, and to assess associated risk factors. METHODS: All consecutive PE patients who were referred to our center in Pisa, Italy between 2001 and 2005 received a conventional initial treatment, followed by vitamin K antagonists [international normalized ratio (INR), 2.0-3.0] for 1 year. They were followed-up at scheduled times at the study center. The development of recurrent PE was objectively documented and recorded. RESULTS: Out of 497 patients, 48 (9.6%) developed recurrent PE, which was fatal in 36. Of these 48 events, 39 occurred within 10 days of diagnosis and only two patients had a non-fatal recurrent PE between 6 and 12 months. Risk factors associated with the risk for overall recurrent PE were persistent severe dyspnoea (P = 0.007), a high perfusion defect score index (PDI) (P = 0.003) and cardiopulmonary co-morbidities (P = 0.005). Unprovoked presentation (P = 0.030), persistent severe dyspnoea (P = 0.011) and a high PDI (P = 0.001) predicted the risk for fatal PE. Overall bleeding incidence was 3.4%, no cases of bleeding occurred between 180 and 360 days post-diagnosis. CONCLUSIONS: In spite of conventional anticoagulation, a proportion of patients with PE experience both a fatal and non-fatal recurrent embolism within the first year. The large majority of these occur within the days proceeding diagnosis, with only a small minority occurring in the last 6 months. No bleeding was observed after 6 months. Therefore, prolonging anticoagulation for 1 year represents both a safe and effective treatment.

The diagnosis of pulmonary embolism.

The diagnosis of pulmonary embolism is challenging, and autoptic series have demonstrated that a high percentage of cases are not recognized ante-mortem. A number of predisposing factors, symptoms and signs associated with pulmonary embolism have been recognized, and should be used to raise the suspicion of the disease. These include immobilization, recent surgery, active cancer, previous thromboembolism, syncope, dyspnoea, chest pain, haemoptysis, signs of deep vein thrombosis, hypocarbic hypoxemia. Once pulmonary embolism is suspected, the clinical probability of the disease should be assessed; to this end, three clinical rules have been proposed and validated (the revised Geneva score, the Wells score and the PISA-PED score) while others await clinical validation. In case of low clinical probability, a negative a D-dimer test is sufficient to rule out the diagnosis, while if the clinical probability is high, or the D-dimer test is positive, further tests are necessary. Computer tomography angiography or perfusion lung scan are the imaging tests of choice, depending on local availability and experience. If the clinical probability and the results of the imaging test are concordant, a definitive diagnosis can be obtained; if the results are discordant, further testing is necessary. In particular, in the specific case of a small clot (i.e. segmental or subsegmental) incidentally recognized at a computer tomography obtained for other reasons in a patient without a clinical suspicion of pulmonary embolism, an occurrence whose frequency is rapidly increasing in clinical practice, a final diagnosis cannot be made without further confirmatory testing.

Abscess formation at the ischiorectal fossa 7 months after the application of a synthetic transobturator sling for stress urinary incontinence in a type II diabetic woman.

A 50-year-old diabetic woman was referred to our unit because of high fever, foul-smelling vaginal discharge and pain in the leg, 7 months after undergoing surgery for application of a transobturator suburethral sling. Patient evaluation revealed erosion of the tape through the vaginal wall; the infection had spread to the region of the internal obturator muscle and then up to the anterior recess of the ischiorectal fossa. The patient underwent surgery for sling removal, antibiotic therapy and, finally, surgical incisions to facilitate drainage of the abscess. All these passages were necessary to obtain complete resolution of the symptoms. Infectious complications are possible after transobturator sling procedures. Patients should then be informed about the risks of erosion and infection and be warned that the appearance of pain and foul-smelling vaginal discharge may indeed be the first symptom of subsequent and much more severe infectious complications.

Minilaparotomy vs laparotomy for uterine myomectomies: a randomized controlled trial.

AIM: To evaluate the efficacy and applicability of the minilaparotomy technique in abdominal myomectomies and to compare it with traditional laparotomy. METHODS: We enrolled 99 women, suffering from symptomatic uterine myomas, to be operated for myomectomy. Through computer randomization, 55 women were assigned to the study group (minilaparotomy) and 44 women to the control group (traditional laparotomy). Women assigned to the study group were operated using a recently modified minilaparotomy technique. Statistical evaluation was performed through Mann-Whitney U test, chi2 test, Student's t-test. RESULTS: Duration of surgery, time for spontaneous recanalization and days of postoperative hospital stay were significantly lower in the study group, as well as treatment satisfaction reported by the patients (p<0.05). Moreover, each minilaparotomy operation ended by saving 620 Euro. CONCLUSIONS: Minilaparotomy seems to be a valid alternative to the removal of symptomatic uterine myomas. The objective and subjective advantages in operated patients, as well as the reduction in sanitary costs are underlined.

Determination of organophosphorus pesticides in honeybees after solid-phase microextraction.

A method based on solid-phase microextraction (SPME) followed by gas chromatography with nitrogen-phosphorus detection was developed for the purpose of determining 18 organophosphorus pesticide residues in honeybee samples (Apis mellifera). The extraction capacities of polyacrylate and poly(dimethylsiloxane) fibers were compared. The main factors affecting the SPME process, such as the absorption time profile, salt, and temperature, were optimized. The method involved honeybee sample homogenization, elution with an acetone:water solution (1:1) and dilution in water prior to fiber extraction. Moreover, the matrix effect on the extraction was evaluated. In samples spiked at the 0.2 mg kg(-1) level, the coefficient variation was between 1 and 13% and the detection limits were below 10 microg kg(-1). The SPME procedure was found to be quicker and more cost-effective than the solvent extraction method commonly used. The method was applied successfully to environmental screening. Parathion methyl was detected and confirmed in the real samples analyzed.

Protection against diabetes by MHC heterozygosity and reversal by cyclophosphamide.

In type I diabetes in both rodents and humans, genetic susceptibility to disease is strongly linked to MHC class II alleles. In some cases, however, certain class II alleles provide resistance to disease. To examine this effect in a well-defined system, we studied double transgenic mice expressing influenza hemagglutinin (HA) on pancreatic islet beta cells and an HA-specific TCR on CD4 T cells. On a susceptible B10.D2 background, 70% of double transgenic mice develop an early-onset spontaneous autoimmune diabetes. MHC heterozygosity induced variable protection from diabetes, depending on the specific nonpermissive allele, but insulitis was invariably present. Autoreactive T cells retained the ability to induce diabetes because cyclophosphamide treatment induced diabetes in 81% of young MHC(d/b) transgenic mice, although the effect was diminished in older mice. Most importantly, treatment induced higher IFN-gamma/IL-4 ratios among CD4 T cells, suggesting a strong shift toward Th1 development, perhaps through direct effects on patterns of gene expression in CD4 T cells.

Expression of relB is required for the development of thymic medulla and dendritic cells.

Dendritic cells (DC) derived from bone marrow are critical in the function of the immune system, for they are the primary antigen-presenting cells in the activation of T-lymphocyte response. Their differentiation from precursor cells has not been defined at a molecular level, but recent studies have shown an association between expression of the relB subunit of the NF-kappa B complex and the presence of DC in specific regions of normal unstimulated lymphoid tissues. Here we show that relB expression also correlates with differentiation of DC in autoimmune infiltrates in situ, and that a mutation disrupting the relB gene results in mice with impaired antigen-presenting cell function, and a syndrome of excess production of granulocytes and macrophages. Thymic UEA-1+ medullary epithelial cells from normal mice show striking similarities to DC and, interestingly, these cells are also absent in relB mutant mice. Taken together, these results suggest that relB is critical in the coordinated activation of genes necessary for the differentiation of two unrelated but phenotypically similar cells (DC and thymic UEA-1+ medullary epithelial cells) and is therefore a candidate for a gene determining lineage commitment in the immune system.

Regulation of CD4 T cell reactivity to self and non-self.

While the thymus may be effective in inducing tolerance to lymphoid associated antigens, it is not as efficient in deleting T cells reactive to peripheral tissue specific antigens. Therefore, to maintain self tolerance to peripheral tissues, post-thymic mechanisms must be invoked. One important way to prevent autoimmune pathology mediated by autoreactive CD4 T cells is the diversion of clones to regulatory Th2 effector cells. However, many different factors contribute in vivo to the decision of stimulated CD4 T cells to develop into Th1 versus Th2 cells. For example, T cell signaling pathways may influence the types of cytokines produced by naive T cells, and studies have provided evidence for a genetic polymorphism among common mouse strains that can significantly influence the early cytokine production in stimulated naive CD4 T cells. The allele carried by the BALB/c strain promotes IL-4 production, and consequently provides resistance to autoimmune diabetes in our transgenic mouse model. In addition, antigen presenting cells can influence the development of stimulated CD4 T cells in part through the production of cytokines such as IL-12. The absorption of IL-12 in vivo can permit the expansion of Th2 type effector cells, and this phenomenon will also protect mice from autoimmunity. Finally, the relative potency of various class II positive antigen presenting cell types can influence the development of autoreactive T cells, with dendritic cells apparently being the strongest stimulator of Th1 responses. Consistent with this notion, a relB knockout mouse, which is missing dendritic cells, appears to drive Th2 development even in response to viral infection. In sum, these various influences over the Th1/Th2 decision in vivo may provide new targets for immunotherapy of autoimmune diseases.

A role for non-MHC genetic polymorphism in susceptibility to spontaneous autoimmunity.

Peripheral immunological tolerance is traditionally explained by mechanisms for deletion or inactivation of autoreactive T cell clones. Using an autoimmune disease model combining transgenic mice expressing a well-defined antigen, influenza hemagglutinin (HA), on islet beta cells (Ins-HA), and a T cell receptor transgene (TCR-HNT) specific for a class II-restricted HA peptide, we demonstrate that the conventional assumptions do not apply to this in vivo situation. Double transgenic mice displayed either resistance or susceptibility to spontaneous autoimmune disease, depending on genetic contributions from either of two common inbred mouse strains, BALB/c or B10.D2. Functional studies on autoreactive CD4+ T cells from resistant mice showed that, contrary to expectations, neither clonal anergy, clonal deletion, nor receptor desensitization was induced; rather, there was a non-MHC-encoded predisposition toward differentiation to a nonpathogenic effector (Th2 versus Th1) phenotype. T cells from resistant double transgenic mice showed evidence for prior activation by antigen, suggesting that disease may be actively suppressed by autoreactive Th2 cells. These findings shed light on functional aspects of genetically determined susceptibility to autoimmunity, and should lead to new therapeutic approaches aimed at controlling the differentiation of autoreactive CD4+ effector T cells in vivo.