The role of regulatory T cells in alloantigen tolerance

Summary: The diversification mechanism used by the adaptive immune system to maximize the recognition of foreign antigens has the side effect of generating autoreactivity. This effect is counteracted by deletion of cells expressing receptors with high affinity to self (central tolerance) and suppression of autoreactive cells by regulatory T cells (Tregs; peripheral tolerance). This understanding led to the notion that Tregs represent a specialized subset of autoreactive T cells with inhibitory function. The process of generating a diverse repertoire of receptors recognizing antigen presented by major histocompatibility complex (MHC) intrinsically leads to the generation of cells recognizing foreign MHC (alloantigen). The precursor frequency of T cells responding to alloantigen is substantially higher than that responding to any exogenous antigen. The only physiological context in which this becomes a problem is placental viviparity. Although the maternal immune system has no intrinsic mechanism to distinguish between a pathogen and paternally derived fetal alloantigen, it has to neutralize the former and tolerate the latter. We review the function of Tregs from this perspective and propose that they may have evolved to promote tolerance to alloantigen in the context of pregnancy.     

Regulatory T cells mediate maternal tolerance to the fetus

Pregnancy constitutes a major challenge to the maternal immune system, as it has to tolerate the persistence of paternal alloantigen. Although localized mechanisms contribute to fetal evasion from immune attack, maternal alloreactive lymphocytes persist. We demonstrate here an alloantigen-independent, systemic expansion of the maternal CD25+ T cell pool during pregnancy and show that this population contains dominant regulatory T cell activity. In addition to their function in suppressing autoimmune responses, maternal regulatory T cells suppressed an aggressive allogeneic response directed against the fetus. Their absence led to a failure of gestation due to immunological rejection of the fetus.     

闭孔疝的临床诊断与治疗

目的:虽然闭孔疝是较为少见的盆腔疝,但极易误诊、漏诊,甚至导致死亡,尤其是老年病人。本文就伴有基础疾病、一般情况欠佳的老年病人,总结了闭孔疝的诊断、治疗和围手术期处理经验。方法:对我院2000年至2010年收治的8例闭孔疝病人的临床资料进行回顾性分析。结果:8例病人均为女性,平均年龄83(77~92)岁,平均体质量指数(BMI)为17.3,术前均以肠梗阻收治入院。2例病人Howship-Romberg征阳性;3例病人通过盆腔CT确诊。8例病人均患有严重的冠心病、高血压和房颤,平均心脏风险指数为34;7例病人ASA-PS评分为3.0~3.5,另1例为4.0。术中发现所有疝的内容物均为小肠肠管;其中4例行小肠肠段切除。全部病人经积极治疗后完全康复;术后随访59个月未见复发。结论:对老年、瘦弱、多产的女性病人,如反复出现不完全性肠梗阻,应高度怀疑闭孔疝,并行腹部和盆腔CT以明确诊断,及早行剖腹探查术可显著降低闭孔疝病人的肠切除率和病死率。     

Study of Left Ventricular Rotation and Torsion in the Acute Phase of ST-Elevation Myocardial Infarction by Speckle Tracking Echocardiography

Background: The mechanics of the complex left ventricular (LV) myocardial fiber architecture may accurately be assessed by speckle tracking echocardiography (STE). The role of STE to assess LV mechanical dysfunction in the setting of ST segment elevation myocardial infarction (AMI) is still poorly studied. Patients and Methods: 29 consecutive patients (55 ± 13 years) presenting with AMI underwent STE within 72 hours of admission. Reperfusion was achieved with thrombolysis in 15 patients and with primary percutaneous coronary intervention in 14. LV rotational and torsion data were registered during peak systole. Standard Doppler data included LV ejection fraction (EF), mitral inflow deceleration time (DT), and conventional E/A ratio. E/E' ratio (mitral inflow E velocity/tissue Doppler E velocity) was calculated as a marker of LV filling pressure. Twelve subjects with clinically indicated but negative dobutamine stress echocardiogram served as Controls. Results: Peak systolic torsion was not only significantly lower in AMI compared with Controls (13.3 ± 7.6 vs. 21.8 ± 6.1; P < 0.01), it was also lower in subjects with LVEF <40% (5.0 ± 2.9) compared with those who had LVEF >40% (10.6 ± 6.6; P < 0.02). Torsion had a modest but significantly positive linear relation (R = 0.6; P < 0.05) with DT, not with E/E' or LVEF. Conclusion: LV systolic torsion is decreased in AMI and more markedly decreased in patients with LVEF <40%. The most significant linear relationship between DT and torsion may possibly indicate that the LV mechanical dysfunction is also associated with altered filling dynamics. (Echocardiography 2010;27:45-49)     

Colchicine attenuates compensation to negative but not to positive lenses in young chicks

Optic nerve-sectioned (ONS) chick eyes are capable of emmetropisation, but these eyes also exhibit increased hyperopia without any visual manipulations, which suggests altered eye growth regulation. These altered growth changes may be related to the loss of retinal ganglion cells that follows nerve lesioning. Colchicine, which also destroys retinal ganglion cells in chicks, was used to further examine the effects of retinal ganglion cell loss on emmetropisation. Growth responses of +10D and -10D lens-wearing colchicine-injected eyes were compared to those of +10D and -10D lens-wearing saline-injected eyes, respectively. Changes after removal of lenses were also analysed. Prior to lens-wear, colchicine-injected eyes exhibited longer optical axial lengths (OL; distance from cornea to retina; p=0.0185) but no differences in refractive error (RE; p=0.6588). Although myopic shifts were not significant for -10D lens-wearing colchicine-injected eyes (p=0.5913), but were for the saline-injected eyes (p=0.0034), these changes were not different (p=0.1646). However, -10D lens-induced OL changes in colchicine-injected eyes showed insignificant (p=0.2214) and reduced (p=0.0102) changes compared to those of saline-injected eyes. +10D lens-treated colchicine-injected eyes showed significant hyperopic shifts (p<0.0001) and significant reductions in OL (p<0.0001) that were similar to those of saline-injected eyes (p=0.7990 and p=0.1495, respectively). Growth responses in eyes recovering from -10D lenses were minimal, with REs unaffected (p=0.3325), but OL reductions affected (p=0.0199) by colchicine. Colchicine-injected eyes recovering from +10D lenses showed significant myopic shifts (p=0.0003) and OL elongations (p<0.0001) that were similar to those of saline-injected eyes (p=0.3999 and p=0.4731, respectively). The results showing that colchicine suppresses the ability to respond to negative lenses but leaves compensation to positive lenses relatively unchanged, are opposite to those of optic nerve sectioned eyes. We speculate that the differences are probably related to the way retinal cells are lost.