Characterization of immune system alterations following preoperative autologous blood donation for elective hip replacement surgery

summary .  Preoperative autologous blood donation (PABD) has been shown to decrease natural killer (NK) cell function in cancer patients, raising concerns about an increased cancer recurrence risk owing to PABD. It is unclear whether PABD leads to other immunomodulatory effects that might affect more short-term risks like postoperative infectious complications in surgical patients. Lymphocyte subsets (CD4+ T cells, CD8+ T cells, B cells, NK cells) were determined in 86 consecutive patients donating 2 units of autologous whole blood prior to elective hip replacement surgery. In addition, cytokine secretion patterns of monocytes [tumour necrosis factor (TNF)] and lymphocytes [interferon-γ, interleukin (IL)-2, IL-4, IL-10] upon stimulation were determined in a random subgroup of 58 patients. Analyses were performed immediately before the first donation and on the day prior to operation. Granulocytes increased during PABD by 4·6% ( P < 0·01). Lymphocytes decreased by 8·8% ( P < 0·01), accompanied by a relative rise in CD4+ T cells by 10·7% ( P < 0·01) and in B cells by 10·3% ( P < 0·01), and a fall of NK cells by 20·8% ( P < 0·01). Stimulated TNF secretion of monocytes was suppressed (−12·3%, P < 0·01). The effect on the reactivity of lymphocytes and the T helper 1 (Th1)/Th2 balance were variable. The observed changes of innate and cellular immunity might influence the risk of perioperative infectious complications.     

Regulation of T helper type 2 cell immunity by interleukin-4 and interleukin-13

Type 2 cytokine responses are typical of immune reactions to parasitic helminth infections, allergies, and asthma, and are characterised by the production of the cytokines interleukin (IL)-4, IL-5, IL-9, and IL-13 by subsets of T helper type 2 (Th2) cells. These cytokines form a complex network of molecular and cellular interactions that mediate protective immunity to worm infection, but also induce inappropriate inflammatory responses to allergic challenge. Although considerable attention has been given to the roles played by IL-4 in Th2 responses, the identification of the related cytokine IL-13 has led to a re-evaluation of how these two molecules combine in the generation of Th2 immunity. Recent reports have highlighted that in certain challenges, IL-4 and IL-13 act in combination to ensure the rapid onset of a Th2-like response. However, these studies have also identified specific responses that are attributable to the individual cytokines. For example, IL-13 appears to play a more dominant role than IL-4 in the expulsion of certain gastrointestinal parasites. In contrast, following schistosome infection, IL-13 induces a detrimental hepatic fibrosis, while IL-4 protects against endotoxemia. These results emphasise the complexity of the cytokine network, and highlight the care that needs to be taken when designing therapeutic intervention.     

Interleukin-10 production by effector T cells: Th1 cells show self control

Interleukin (IL)-10 is a cytokine that modulates both innate and adaptive immunity, primarily by exerting antiinflammatory effects. IL-10 was originally thought to be produced only by T helper (Th)2 cells, but is now known to be made by a variety of cell types. During many infections, CD4(+) T cells produce both interferon (IFN)-gamma, the signature Th1 cytokine, and IL-10. New data now show that the IL-10 produced by effector Th1 cells helps limit the collateral damage caused by exaggerated inflammation. But this control may also limit the effectiveness of the immune response, resulting in a failure to fully eliminate pathogens.     

Immunologic changes after transfusion of autologous or allogeneic buffy coat-poor versus white cell-reduced blood to patients undergoing arthroplasty. I. Proliferative T-cell responses and the balance of helper and suppressor T cells

BACKGROUND: Donor white cells (WBCs) contained in red cell (RBC) transfusions are thought to provoke down-regulation of T-cell-mediated immunity. This study investigated this topic in otherwise healthy patients receiving buffy coat-depleted or WBC-filtered RBCs and undergoing standardized perioperative management. STUDY DESIGN AND METHODS: Patients undergoing elective orthopedic surgery (primary hip and knee replacement surgery) were enrolled in a prospective study. Perioperative changes in T-cell proliferation (stimulation with phytohemagglutinin and mixed lymphocyte culture) and T-cell balance (T-lymphocytes, helper T cells, and suppressor T cells) were compared after random assignment to allogeneic buffy coat-depleted (Group 2, n = 8) or WBC-reduced RBC (Group 3, n = 11) transfusion regimens. Recipients of autologous buffy coat-depleted RBC transfusions (n = 15) served as controls (Group 1). RESULTS: Compared to that in autologous transfusion recipients, alloantigen-induced T-cell proliferation was significantly reduced in recipients of allogeneic WBC-reduced RBCs (Day 3, p = 0.0274). After the transfusion of allogeneic buffy coat-depleted RBCs, a weak trend toward decreased T-cell proliferation was observed (p = 0.0933) and the numbers of CD4+ T cells were also significantly lower (Day 7, p = 0.0389). On Day 10, alloantigen-induced T-cell proliferation remained significantly below baseline after transfusion of WBC-reduced RBCs (p = 0.05), the numbers of CD3+ cells decreased in allogeneic RBC recipients (Group 2, p = 0.078; Group 3, p = 0.05), and those of CD8+ cells decreased significantly after the transfusion of allogeneic buffy coat-depleted RBCs (p = 0.0234) concomitant with an increased CD4:CD8 ratio (p = 0.0391). CONCLUSION: Results of the present study confirm the hypothesis of impaired T-cell-mediated immunity after allogeneic transfusion.     

Resting Respiratory Tract Dendritic Cells Preferentially Stimulate T Helper Cell Type 2 (Th2) Responses and Require Obligatory Cytokine Signals for Induction of ?Th1 Immunity

Consistent with their role in host defense, mature dendritic cells (DCs) from central lymphoid organs preferentially prime for T helper cell type 1 (Th1)-polarized immunity. However, the “default” T helper response at mucosal surfaces demonstrates Th2 polarity, which is reflected in the cytokine profiles of activated T cells from mucosal lymph nodes. This study on rat respiratory tract DCs (RTDCs) provides an explanation for this paradox. We demonstrate that freshly isolated RTDCs are functionally immature as defined in vitro, being surface major histocompatibility complex (MHC) II ^lo, endocytosis^hi, and mixed lymphocyte reaction^lo, and these cells produce mRNA encoding interleukin (IL)-10. After ovalbumin (OVA)-pulsing and adoptive transfer, freshly isolated RTDCs preferentially stimulated Th2-dependent OVA-specific immunoglobulin (Ig)G₁ responses, and antigen-stimulated splenocytes from recipient animals produced IL-4 in vitro. However, preculture with granulocyte/macrophage colony stimulating factor increased their in vivo IgG priming capacity by 2–3 logs, inducing production of both Th1- and Th2-dependent IgG subclasses and high levels of IFN-γ by antigen-stimulated splenocytes. Associated phenotypic changes included upregulation of surface MHC II and B7 expression and IL-12 p35 mRNA, and downregulation of endocytosis, MHC II processing– associated genes, and IL-10 mRNA expression. Full expression of IL-12 p40 required additional signals, such as tumor necrosis factor α or CD40 ligand. These results suggest that the observed Th2 polarity of the resting mucosal immune system may be an inherent property of the resident DC population, and furthermore that mobilization of Th1 immunity relies absolutely on the provision of appropriate microenvironmental costimuli.     

CpG Oligodeoxynucleotides Act as Adjuvants that Switch on T Helper 1 (Th1) Immunity

Synthetic oligodeoxynucleotides (ODN) that contain unmethylated CpG motifs (CpG ODN) induce macrophages to secrete IL-12, which induces interferon (IFN)-γ secretion by natural killer (NK) cells. Since these cytokines can induce T helper 1 (Th1) differentiation, we examined the effects of coadministered CpG ODN on the differentiation of Th responses to hen egg lysozyme (HEL). In both BALB/c (Th2-biased) and B10.D2 (Th1-biased) mice, immunization with HEL in incomplete Freund's adjuvant (IFA) resulted in Th2-dominated immune responses characterized by HEL-specific secretion of IL-5 but not IFN-γ. In contrast, immunization with IFA-HEL plus CpG ODN switched the immune response to a Th1-dominated cytokine pattern, with high levels of HEL-specific IFN-γ secretion and decreased HEL-specific IL-5 production. IFA-HEL plus CpG ODN also induced anti-HEL IgG2a (a Th1-associated isotype), which was not induced by IFA-HEL alone. Control non–CpG ODN did not induce IFN-γ or IgG2a, excepting lesser increases in B10.D2 (Th1-biased) mice. Thus, CpG ODN provide a signal to switch on Th1-dominated responses to coadministered antigen and are potential adjuvants for human vaccines to elicit protective Th1 immunity.     

The effect of unmodified or prestorage white cell-reduced allogeneic red cell transfusions on the immune responsiveness in orthopedic surgery patients

BACKGROUND: The immunomodulatory effects of allogeneic blood transfusions have been attributed to the white cells (WBCs) present in the cellular blood components transfused to patients. STUDY DESIGN AND METHODS: The effect of the transfusion of allogeneic red cells (RBCs) or allogeneic prestorage WBC-reduced RBCs (WBC-reduced RBCs) on host immune responsiveness was evaluated by measuring the lymphocyte subsets and the in-vitro cytokine production in response to phytohemagglutinin stimulation of WBCs of orthopedic surgery patients. Forty-seven patients undergoing hip replacement surgery were randomly assigned to receive allogeneic RBCs (n = 17) or WBC-reduced RBCs (n = 14; 99.95% WBC removal). Sixteen patients were not transfused. Patient blood samples taken before surgery and on Days 1 and 4 after surgery were tested for complete blood count, lymphocyte subset analysis, and measurement of cytokine levels. RESULTS: After surgery, the lymphocyte count was significantly decreased in patients transfused with > or = 3 units of allogeneic RBCs (2.0 +/- 0.5 vs. 1.3 +/- 0.3 x 10(9)/L; p = 0.017), but not in patients transfused with > or = 3 units of WBC-reduced RBCs (2.0 +/- 0.9 vs. 1.7 +/- 0.8 x 10(9)/L). Compared with preoperative levels, on Day 4 after surgery, patients transfused with > or = 3 units of allogeneic RBCs also had a decrease in the number of natural killer cells (0.07 +/- 0.05 vs. 0.04 +/- 0.03 x 10(9)/L; p = 0.018). Postoperatively, interleukin-2 was decreased in one patient who received WBC-reduced RBCs compared with that in four patients transfused with allogeneic RBCs (p = 0.32), and eight untransfused patients (p = 0.01). On Day 4, about 70 percent of patients transfused with allogeneic RBCs showed a 20-percent decrease in the interferon gamma level. CONCLUSION: Taken together, these data support the hypothesis that transfusion of > or = 3 units of allogeneic RBCs is associated with early postoperative lymphopenia in otherwise healthy individuals undergoing surgery. These findings were not observed in those individuals transfused with RBCs that had undergone prestorage WBC reduction.     

CD4~+辅助性T细胞及其细胞因子与肝移植后的免疫

目的:就CD4~+辅助性T细胞(Th)及其细胞因子与移植免疫状态的关系及研究现状作一综述.资料来源:由第一作者进行检索.检索时限及数据库:Medline数据库1970-01/2008-12,万方医学网1998-01/2008-12,中国医院知识仓库1998-01/2008-12.英文检索词为"liver transplantation, rejection,immune tolerance,T helper lymphocytes, Th1 cells, Th2 cells";中文检索词为"肝移植,排斥反应,免疫耐受,辅助性T淋巴细胞,Th1细胞,Th2细胞".资料选择:纳入描述肝移植后免疫状态及辅助性T细胞及其细胞因子作用的文献,排除综述文献及重复研究类文章.结局评价指标:对资料进行初审,选取相关文献查找全文,纳入36篇.其中有关辅助性T细胞及移植后免疫状态研究背景的文献3篇,有关Th细胞及其细胞因子在移植免疫中作用的文献22篇,有关Th细胞及其细胞因子与移植免疫关系的文献11篇.结果:Th细胞是调节机体免疫应答的一类重要调节性细胞,具有辅助体液和细胞免疫的功能,Th细胞及其细胞因子在肝移植免疫中起十分重要的作用,Th1/Th2的平衡与肝移植后免疫反应密切相关,Th1细胞因子分泌增加可致肝脏排斥反应,当Th1/Th2向Th2偏移,易发生免疫耐受反应.结论:迄今为止,Th1/Th2转换与移植免疫关系的研究只停留在实验水平,如何将其学说应用于临床实践,通过检测和调整细胞因子等方法来确定机体的免疫状态,调节Th1/Th2的分化,从而诱导宿主的特异性免疫耐受应该成为下一步研究的重点.     

Plasmapheresis affects T helper type-1/T helper type-2 balance of circulating peripheral lymphocytes.

Plasmapheresis not only removes humoral factors, but may also modulate cellular immunity. We investigated whether plasmapheresis influenced T helper type-1/T helper type-2 (Th1/Th2) cytokine-producing-cell balance in 3 patients with neuroimmunological disease. The production of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and IL-4 in the culture supernatant of peripheral blood mononuclear cells stimulated by anti-CD3 and anti-CD28 was assayed. In 2 of 3 patients, plasmapheresis (immunoadsorption or plasma exchange) reduced Th1/Th2 cytokine ratio. The results may suggest that plasmapheresis induces a shift of Th1/Th2 balance in peripheral blood.     

Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells

The mechanisms by which immune responses to nonpathogenic environmental antigens lead to either allergy or nonharmful immunity are unknown. Single allergen-specific T cells constitute a very small fraction of the whole CD4+ T cell repertoire and can be isolated from the peripheral blood of humans according to their cytokine profile. Freshly purified interferon-gamma-, interleukin (IL)-4-, and IL-10-producing allergen-specific CD4+ T cells display characteristics of T helper cell (Th)1-, Th2-, and T regulatory (Tr)1-like cells, respectively. Tr1 cells consistently represent the dominant subset specific for common environmental allergens in healthy individuals; in contrast, there is a high frequency of allergen-specific IL-4-secreting T cells in allergic individuals. Tr1 cells use multiple suppressive mechanisms, IL-10 and TGF-beta as secreted cytokines, and cytotoxic T lymphocyte antigen 4 and programmed death 1 as surface molecules. Healthy and allergic individuals exhibit all three allergen-specific subsets in different proportions, indicating that a change in the dominant subset may lead to allergy development or recovery. Accordingly, blocking the suppressor activity of Tr1 cells or increasing Th2 cell frequency enhances allergen-specific Th2 cell activation ex vivo. These results indicate that the balance between allergen-specific Tr1 cells and Th2 cells may be decisive in the development of allergy.     

免疫调节性细胞及其效应分子在CITP免疫功能紊乱中的作用研究

目的探讨调节性T细胞(Treg)、调节性B细胞(Breg)、辅助性T细胞17(Th17)、辅助性T细胞22(Th22)及其相关细胞因子的变化在慢性特发性血小板减少性紫癜(CITP)患者免疫功能紊乱中的作用。方法选择CITP患者40例、健康者40例,分离外周血单个核细胞,采用流式细胞术检测Treg、Breg、Th17、Th22细胞数量与比例,采用酶联免疫吸附法检测血浆中白细胞介素10(IL-10)、转化生长因子β1(TGF-β1)、白细胞介素17(IL-17)、白细胞介素(IL-22)水平,计算IL-17/IL-10、IL-22/TGF-β1比值。比较CITP患者、健康者各指标检测结果。结果 CITP患者Th17、Th22细胞及IL-17、IL-22水平高于健康者,Treg、Breg细胞及IL-10、TGF-β1水平低于健康者(P0.05)。CITP患者Th17/Treg、Th22/Breg、IL-17/IL-10、IL-22/TGF-β1比值水平均高于健康者(P0.05)。结论 Th17、Treg、Th22、Breg细胞水平异常及IL-17/IL-10、IL-22/TGF-β1比值变化可能与CITP患者免疫功能紊乱密切相关。     

血清IL-10和IL-12在自身免疫性甲状腺疾病中的表达特征

目的：研究自身免疫性甲状腺疾病中血清白细胞介素－10（IL－10）和白细胞介素－12（IL－12）的表达特征及其在免疫反应发生中的作用和机制。方法：对38例Graves病（GD）患者（18例未治疗的初诊患者，为GDa组；20例抗甲亢药物治疗的患者，为GDb组）、24例慢性淋巴细胞性甲状腺炎（HD）患者及22例正常者（对照组）检测了血清中IL－10，IL－12的表达水平及甲状腺功能的变化。IL－10和IL－12采用酶联免疫法（ELISA）测定。血清游离T3（FT3），游离T4（FT4）和促甲状腺激素（TSH）测定用化学发光免疫分析法。抗甲状腺球蛋白抗体（TgAb)和抗甲状腺微粒体抗体（TmAb)用放射免疫法。结果：GDa组的IL－10、IL－12均高于对照组（P＜0．05，P＜0．01），但以IL－12的增高占优势，IL－12／IL－10比值增高（P＜0．05）。GDb组的IL－12水平和IL－12／IL－10比值较GDa组显著降低（P＜0．05，P＜0．01），与对照组比较无显著差异。IL－10水平较GDa组有上升趋势但无统计学意义，但高于对照组（P＜0．01），HD患者IL－12水平和IL－12／IL－10比值均较对照组增高（P＜0．01，P＜0．01），较GDb组也显著增高（P＜0．05，P＜0．01），IL－10水平与对照组比较无显著差异，但显著低于GDb组（P＜0．05）。结论：GD患者，在甲状腺功能亢进状态时，由Thl细胞产生的IL－12水平和低表Th2细胞活力的IL－10水平均明显增高，提示Th1和Th2的表达均增高，细胞免疫和体液免疫均参入了甲亢的自身免疫反应过程。在HD患者也有IL－12水平的显著增高，表明了Th1细胞因子所介导的细胞免疫在HD的病理反应中起主导作用。在GD和HD患者，均表现有IL－12／IL－10比值的变化，提示Th1/Th2间的平衡紊乱可能对介导甲状腺自身免疫炎症反应的产生起关键作用。     

Altered Immune Responses in Interleukin 10 Transgenic Mice

Interleukin (IL)-10 is a pleiotropic cytokine which inhibits a broad array of immune parameters including T helper cell type 1 (Th1) cytokine production, antigen presentation, and antigenspecific T cell proliferation. To understand the consequences of altered expression of IL-10 in immune models of autoimmune disease, the response to infectious agents, and the response to tumors, we developed transgenic mice expressing IL-10 under the control of the IL-2 promoter. Upon in vitro stimulation, spleen cells from unimmunized transgenic mice secrete higher levels of IL-10 and lower amounts of IFN-γ than do controls, although no gross abnormalities were detected in lymphocyte populations or serum Ig levels. Transfer of normally pathogenic CD4⁺ CD45RB^high splenic T cells from IL-10 transgenic mice did not cause colitis in recipient severe combined immunodeficiency mice. Furthermore, co-transfer of these transgenic cells with CD4⁺ CD45RB^high T cells from control mice prevented disease. Transgenic mice retained their resistance to Leishmania major infection, indicating that their cell-mediated immune responses were not globally suppressed. Lastly, in comparison to controls, IL-10 transgenic mice were unable to limit the growth of immunogenic tumors. Administration of blocking IL-10 mAbs restored in vivo antitumor responses in the transgenic mice. These results demonstrate that a single alteration in the T cell cytokine profile can lead to dramatic changes in immune responses in a manner that is stimulus dependent. These mice will be useful in defining differences in inflammatory conditions and cellular immunity mediated by IL-10.     

Type 2 immunity is controlled by IL-4/IL-13 expression in hematopoietic non-eosinophil cells of the innate immune system

Nippostrongylus brasiliensis infection and ovalbumin-induced allergic lung pathology are highly interleukin (IL)-4/IL-13 dependent, but the contributions of IL-4/IL-13 from adaptive (T helper [Th]2 cells) and innate (eosinophil, basophils, and mast cells) immune cells remain unknown. Although required for immunoglobulin (Ig)E induction, IL-4/IL-13 from Th2 cells was not required for worm expulsion, tissue inflammation, or airway hyperreactivity. In contrast, innate hematopoietic cell–derived IL-4/IL-13 was dispensable for Th2 cell differentiation in lymph nodes but required for effector cell recruitment and tissue responses. Eosinophils were not required for primary immune responses. Thus, components of type 2 immunity mediated by IL-4/IL-13 are partitioned between T cell–dependent IgE and an innate non-eosinophil tissue component, suggesting new strategies for interventions in allergic immunity.     

Increased levels of soluble ST2 protein and IgG1 production in patients with sepsis and trauma

Objective T1/ST2, a member of the interleukin (IL)-1 receptor superfamily, is predominantly expressed on type-2 T helper (Th2) cells but not Th1 cells, and plays a role in cell proliferation and Th2 immune response. The relation of soluble ST2, Th1-Th2 cytokine profile, and immunoglobulin (Ig) production in sepsis and trauma patients is not well known.Design and setting Case-control study at a university hospital intensive care unit.Patients Fifteen patients recruited within 24–48 h of diagnosis of sepsis, 13 trauma patients recruited within 24 h after admission to the ICU, 11 patients who underwent abdominal surgery, and 15 healthy volunteers served as control.Measurements and results ELISA was utilized to detect serum soluble ST2, IL-2, IFN-, IL-10, and Ig production. Serum levels of soluble ST2 were significantly increased in septic patients (8420±2169 pg/ml) as compared with trauma (2936±826 pg/ml), abdominal surgery (1423±373 pg/ml), and healthy controls (316±72 pg/ml; p<0.001, respectively). These results were accompanied by an increase of IgG1 and IgG2 production, and decrease of IL-2 and IFN- synthesis in septic patients. IL-10 was significantly increased in both septic and trauma patients.Conclusions Our results demonstrate that soluble ST2, a marker for Th2 cytokine producing cells, is increased in sepsis and trauma patients, and they provide further evidence for a shift from Th1- to Th2-biased cells.     

同种输血对食管癌患者围手术期细胞因子的影响

目的　探讨同种输血对食管癌患者细胞因子生成的影响及相互关系。方法　食管癌患者手术常规输血18例 ,去白细胞输血 14例 ,采用生物素 亲和素系统测定技术检测患者围手术期常规输血和去白细胞输血后血清中IL 10、IFN γ和TNF α的浓度。结果　常规输血后第 1天与输血前相比血清中IL 10、IFN γ和TNF α浓度升高 ,且以IL 10、IFN γ变化尤为显著 ;输血后第 5天IFN γ和TNF α降低接近输血前水平 ,并明显低于去白细胞输血组 ,IL 10仍明显高于输血前水平。去白细胞输血后不同时间IL 10无显著性改变。结论　食管癌患者围手术期同种输血后血清中IFN γ和TNF α的降低与IL 10升高有关 ,而IL 10升高可能是患者同种输血后免疫抑制的最重要原因 ,输注去白细胞血液可减轻或去除这一作用。     

Selection of a human T helper type 1-like T cell subset by mycobacteria

Mycobacteria elicit a cellular immune response in their hosts. This response usually leads to protective immunity, but may sometimes be accompanied by immunopathology due to delayed type hypersensitivity (DTH). A striking example in man is tuberculoid leprosy, which is characterized by high cellular immunity to Mycobacterium leprae and immunopathology due to DTH. Skin lesions of patients suffering from this disease have the characteristics of DTH reactions in which macrophages and CD4+ T lymphocytes predominate. In animal models, it has been shown that DTH responses are associated with the presence of a particular subset of CD4+ T cells (T helper type 1 [Th1]) that secrete only certain cytokines, such as interleukin 2 (IL-2), interferon gamma (IFN-gamma), and lymphotoxin, but no IL-4 or IL-5. We studied the cytokine release of activated M. leprae-reactive CD4+ T cell clones derived from tuberculoid leprosy patients. These T cell clones, which were reactive with mycobacterial heat shock proteins, exhibited a Th1-like cytokine secretion pattern with very high levels of IFN-gamma. Half of these clones secreted low levels of IL-4 and IL-5, but the ratio of IFN-gamma to IL-4 and IL-5 was much higher than that of T cell clones reactive with nonmycobacterial antigens. A Th1-like cytokine secretion pattern was also observed for T cell clones and polyclonal T cell lines from control individuals that recognized both heat shock and other mycobacterial antigens. The levels of IFN-gamma secreted by these clones were, however, significantly less than those of patient-derived T cell clones. This Th1-like pattern was not found with T cell clones from the same patients and healthy individuals generated in the same manner, but reactive with nonmycobacterial antigens. Our data thus indicate that mycobacteria selectively induce human T cells with a Th1-like cytokine secretion profile.     

Both L3T4+ and Lyt-2+ helper T cells initiate cytotoxic T lymphocyte responses against allogenic major histocompatibility antigens but not against trinitrophenyl-modified self

This study characterizes the T helper (Th) cells that initiate primary cytotoxic T lymphocyte (CTL) responses against allogeneic and trinitrophenyl (TNP)-modified self class I major histocompatibility (MHC) determinants. We show that two distinct Th cell subsets participate in allospecific CTL responses: (a) an L3T4+,Lyt-2- class II-restricted Th cell population, and (b) an L3T4-,Lyt-2+ class I-restricted Th cell population. Both of these T cell subpopulations were shown to function in allospecific CTL responses as helper cells by their ability to show synergy with allospecific CTL precursors. Thus, primary class I allospecific CTL responses represent an immune response involving not only L3T4+ Th cells, but Lyt-2+ Th cells as well. One of the necessary functions performed by both L3T4+ and Lyt-2+ Th cell populations in allospecific CTL responses was found to be the secretion of interleukin 2. Finally, despite the many similarities between anti-allo- and anti-TNP-CTL responses, anti-TNP-CTL responses were found to be mediated by only L3T4+ Th cells, not by Lyt-2+ Th cells. Consequently, Lyt-2+ Th cells appear to be a helper cell population that is primarily involved in MHC-specific immune responses.     

Influenza virus-specific CD4+ T helper type 2 T lymphocytes do not promote recovery from experimental virus infection

T lymphocytes play a primary role in recovery from viral infections and in antiviral immunity. Although viral-specific CD8+ and CD4+ T cells have been shown to be able to lyse virally infected targets in vitro and promote recovery from lethal infection in vivo, the role of CD4+ T lymphocytes and their mechanism(s) of action in viral immunity are not well understood. The ability to further dissect the role that CD4+ T cells play in the immune response to a number of pathogens has been greatly enhanced by evidence for more extensive heterogeneity among the CD4+ T lymphocytes. To further examine the role of CD4+ T cells in the immune response to influenza infection, we have generated influenza virus-specific CD4+ T cell clones from influenza-primed BALB/c mice with differential cytokine secretion profiles that are defined as T helper type 1 (Th1) clones by the production of interleukin 2 (IL-2) and interferon gamma (IFN-gamma), or as Th2 clones by the production of IL-4, IL-5, and IL-10. Our studies have revealed that Th1 clones are cytolytic in vitro and protective against lethal challenge with virus in vivo, whereas Th2 clones are noncytolytic and not protective. Upon further evaluation of these clonal populations we have shown that not only are the Th2 clones nonprotective, but that pulmonary pathology is exacerbated as compared with control mice as evidenced by delayed viral clearance and massive pulmonary eosinophilia. These data suggest that virus-specific CD4+ T cells of the Th2 subset may not play a primary role in virus clearance and recovery and may lead to immune mediated potentiation of injury.     

CD4^＋辅助性T细胞及其细胞因子与肝移植后的免疫

目的：就CD4^＋辅助性T细胞（Th）及其细胞因子与移植免疫状态的关系及研究现状作一综述。资料来源：由第一作者进行检索。检索时限及数据库：Medline数据库1970-01/2008-12,万方医学网1998-01/2008-12,中国医院知识仓库1998-01/2008-12。英文检索词为＂liver transplantation,rejection,immune tolerance,T helper lymphocytes,Th1 cells,Th2cells＂;中文检索词为＂肝移植,排斥反应,免疫耐受,辅助性T淋巴细胞,Th1细胞,Th2细胞＂。资料选择：纳入描述肝移植后免疫状态及辅助性T细胞及其细胞因子作用的文献,排除综述文献及重复研究类文章。结局评价指标：对资料进行初审,选取相关文献查找全文,纳入36篇。其中有关辅助性T细胞及移植后免疫状态研究背景的文献3篇,有关Th细胞及其细胞因子在移植免疫中作用的文献22篇,有关Th细胞及其细胞因子与移植免疫关系的文献11篇。结果：Th细胞是调节机体免疫应答的一类重要调节性细胞,具有辅助体液和细胞免疫的功能,Th细胞及其细胞因子在肝移植免疫中起十分重要的作用,Th1/Th2的平衡与肝移植后免疫反应密切相关,Th1细胞因子分泌增加可致肝脏排斥反应,当Th1/Th2向Th2偏移,易发生免疫耐受反应。结论：迄今为止,Th1/Th2转换与移植免疫关系的研究只停留在实验水平,如何将其学说应用于临床实践,通过检测和调整细胞因子等方法来确定机体的免疫状态,调节Th1/Th2的分化,从而诱导宿主的特异性免疫耐受应该成为下一步研究的重点。