Cytokeratin positive T cell malignant lymphoma.

A high grade T cell malignant lymphoma is described in which weak staining of tumour cells for leucocyte common antigen and T cell markers coexisted with strong positive cytoplasmic staining with the anticytokeratin marker CAM 5.2. This is the first report of non-CD30 positive T cell lymphoma showing cytokeratin positivity. On ultrastructural examination there was no evidence of epithelial differentiation or of accumulation of cytokeratin-type intermediate filaments. The case adds to the range of malignant lymphomas which can, on rare occasions, show cytokeratin positivity. Pathologists should be aware of this potential diagnostic pitfall if inappropriate investigations and therapeutic regimens are to be avoided.     

Differentiation between cutaneous form of adult T cell leukemia/lymphoma and cutaneous T cell lymphoma by in situ hybridization using a human T cell leukemia virus-1 DNA probe.

Adult T cell leukemia/lymphoma (ATLL) shares overlapping clinicopathological features with cutaneous T cell lymphoma (CTCL), requiring detection of monoclonal integration of proviral DNA of type 1 human T cell leukemia virus for its differential diagnosis from the latter. We applied in situ hybridization (ISH) and polymerase chain reaction (PCR) to paraffin sections from 63 Japanese autopsy cases that had been diagnosed as CTCL in earlier years when ATLL was still not widely known. Eleven and two cases with confirmed diagnoses of ATLL and CTCL served as positive and negative controls, respectively. It was found that ISH was positive in 7 of 63 test cases and 10 of 11 positive controls, whereas PCR was positive in none of the test cases and eight of the positive control cases. Two negative controls were negative for both ISH and PCR. We conclude that ISH is superior to PCR for detecting type 1 human T cell leukemia virus proviral DNA on paraffin sections and that the ISH method is useful for differentiating CTCL from the cutaneous form of ATLL.     

CK阳性T细胞淋巴瘤1例报道并文献复习

目的 研究CK呈阳性表达的非霍奇金小T细胞性淋巴瘤的病理学特征及鉴别诊断。方法 运用光镜、电镜及免疫组化技术，观察1例CK呈阳性表达非霍奇金小T细胞性淋巴瘤的组织学、超微结构形态及免疫组化特征并复习相关文献。结果 肿瘤组织主由弥漫分布的小圆形细胞构成。核仁不明显。CD45、CD45RO、和CK(广谱、低分子量、高分子量和19、)均为( )。CD20和CD79均为(-)。电镜观察瘤细胞胞核圆形，居中。胞质少．可见线粒体．未见上皮细胞分化特征、神经内分泌颗粒。结论 非霍奇金小T细胞性淋巴瘤偶可呈CK阳性表达，在应用免疫组化技术对低分化肿瘤进行鉴别诊断时应注意肿瘤组织的异常表达。     

Transformation of cutaneous T cell lymphoma to large cell lymphoma. A clinicopathologic and immunologic study.

Some patients with cutaneous T cell lymphoma (CTCL) develop a high-grade, large-cell lymphoma associated with rapid deterioration of clinical status. This change in histologic appearance and clinical behavior of CTCL is similar to transformations of other hematopoietic and lymphoid neoplasms. From a group of 92 cases of CTCL, morphologic, immunologic and clinical features were studied in 17 cases of transformed CTCL. Transformation was noted, at presentation or subsequently, in either cutaneous or extracutaneous sites; remarkably, transformation was found at initial diagnosis of CTCL in 7 of 17 patients. T cell characteristics were maintained in all 17 cases of transformed CTCL; in 11 cases with complete phenotypes, there were 6 T-helper, 3 T-suppressor, and 2 aberrant T subtypes. The pre- and posttransformation phenotypes were similar in 3 of 7 cases tested over time (all T-helper); retention of T-suppressor phenotype was suggested in another case. T cell features were maintained in the other 3 cases, but the T subtypes were altered in 2 of these cases. Absent or diminished pan-T antigens (CD 5, CD 3, or UCHL1) were found in 9 of 17 cases. Leu-M1, Ki-1, or LN 2 antigens were expressed by transformed cells in 10 of 17 cases, often in patterns identical to Reed-Sternberg cells. Survival in patients with transformed CTCL was significantly shorter (median, 29 months) than in 44 CTCL patients without transformation (58 months, P = 0.015); survival after diagnosis of transformation was short (12 months). Patients with extracutaneous transformation had a shorter median survival after transformation (8 months) than those with transformation limited to skin (19 months). It is concluded that CTCL can transform morphologically to a large cell variant associated with aggressive behavior and shortened survival. Extracutaneous transformation apparently indicates a poorer prognosis than cutaneous transformation. Although transformed CTCL usually retains a T cell phenotype, some antigens are lost while other new antigens may be expressed. Recognition of transformed CTCL is facilitated by identification of the dysplastic cerebriform cell component, but often requires correlation of immunologic and clinical features.     

T淋巴瘤EL-4细胞双受体表达研究

目的:检测T淋巴瘤EL-4细胞T细胞受体(T cell receptor,TCR)的表达情况,为进一步研究T细胞等位基因排斥机制奠定基础。方法:以小鼠脾细胞作为阳性对照,分别提取脾细胞和EL-4细胞mRNA,逆转录为cDNA,RT-PCR扩增24个TCR BV家族CDR3区,结合基因扫描(GeneScan)和基因测序技术,对有表达的TCR BV家族进行CDR3谱型和序列分析。结果:小鼠脾细胞24 BV家族均有表达,各TCR BV家族CDR3谱型均呈高斯分布(Gaussian distribution),表明24 BV家族均为多克隆性。EL-4细胞被同时检测到TCR BV10和BV12家族表达,CDR3谱型均呈单峰,两个家族的RT-PCR产物经测序鉴定证实确属TCR序列,且均为框内编码。结论:EL-4细胞存在两套框内重排的TCRβ链,表明其TCRβ链可能存在等位基因排斥"缺陷"现象。本研究为探索T细胞等位基因排斥机制奠定了基础。     

免疫杀伤细胞治疗对恶性肿瘤患者T淋巴细胞免疫功能的影响

目的 探讨链式激活和诱导的免疫杀伤细胞(CAPRI细胞)治疗对肿瘤患者T淋巴细胞免疫功能的影响.方法 接受CAPRI细胞治疗的滨州医学院附属医院肿瘤内科收治的50例恶性肿瘤患者为研究对象(肿瘤组),同时选择体检健康者30例为对照组,用流式细胞术检测所有患者治疗前后外周血T淋巴细胞CD3+及CD4+、CD8+的百分率,计算CD4+/CD8+比值并进行比较.结果 肿瘤患者治疗前外周血CD3+、CD4+、CD8+、CD4+/CD8+[ (56.40±7.14)％、(30.69±8.01)％、(29.10±7.13)％、1.05 ±0.28]与健康对照组[(66.78±6.05)％、(41.35±5.71)％、(26.08±5.36)％、1.59±0.31]及治疗后13 d[ (59.35±6.31)％、(34.95±7.21)％、(27.95±6.03)％、1.25±0.22]和治疗后25d[(62.36±6.41)％、(37.03±7.62)％、( 25.04±4.53)％、1.46±0.48]比较,CD3+、CD4+、CD4+/CD8+均明显降低、CD8+均明显升高(均P＜0.05);治疗后25d与治疗后13d比较,CD3+、CD4+、CD4+/CD8+均明显升高、CD8+均明显降低(均P＜0.05).结论 CAPRI细胞治疗肿瘤,能够纠正CD3+、CD4+、CD8+、CD4+/CD8+失衡状态,能够调节机体T淋巴细胞的免疫功能.     

The role of T cells in cutaneous autoimmune disease

T cells assume a fundamental function in immunosurveillance and maintenance of the cutaneous immune barrier, yet derangement of their requisite role effects a range of cutaneous autoimmune diseases with significant associated morbidity. While blistering skin diseases, such as pemphigus vulgaris (PV), pemphigus foliaceus (PF) and bullous pemphigoid (BP) are mediated by antibodies directed against autoantigens found in the skin, recent evidence has shown that T cell activation is crucial for the initiation and coordination of this humoral response. Non-blistering skin diseases, such as alopecia areata (AA), vitiligo (VL) and psoriasis (PS) are increasingly believed to be directly mediated by the activities of autoreactive T cells. Here, we examine T lymphocyte control of antibody-mediated and cell-mediated processes involved in the pathoimmunology of the above mentioned skin diseases.     

The role of T cells in cutaneous autoimmune disease

T cells assume a fundamental function in immunosurveillance and maintenance of the cutaneous immune barrier, yet derangement of their requisite role effects a range of cutaneous autoimmune diseases with significant associated morbidity. While blistering skin diseases, such as pemphigus vulgaris (PV), pemphigus foliaceus (PF) and bullous pemphigoid (BP) are mediated by antibodies directed against autoantigens found in the skin, recent evidence has shown that T cell activation is crucial for the initiation and coordination of this humoral response. Non-blistering skin diseases, such as alopecia areata (AA), vitiligo (VL) and psoriasis (PS) are increasingly believed to be directly mediated by the activities of autoreactive T cells. Here, we examine T lymphocyte control of antibody-mediated and cell-mediated processes involved in the pathoimmunology of the above mentioned skin diseases.     

Modulation of dendritic cell and T cell cross-talk during aging: The potential role of checkpoint inhibitory molecules

Dendritic cells (DCs) undergo continuous changes throughout life, and there is evidence that elderly DCs have a reduced capacity to stimulate T cells, which may contribute to impaired anti-tumour immune responses in elderly people with cancer. Changes in checkpoint inhibitory molecules/pathways during aging may be one mechanism that impairs the ability of elderly DCs to activate T cells. However, little is currently known regarding the combined effects of aging and cancer on DC and T cell inhibitory molecules/pathways. In this review, we discuss our current understanding of the influence of aging and cancer on key DC and T cell inhibitory molecules/pathways, the potential underlying cellular and molecular mechanisms contributing to their modulation, and the possibility of therapeutically targeting inhibitory molecules in elderly cancer patients.     

T cell receptor beta-chain gene rearrangement without gamma-chain gene rearrangement in cutaneous T cell lymphoma: an unusual finding

T cells from the blood and skin of a patient with cutaneous T cell lymphoma demonstrated rearrangement of the T cell receptor beta-chain gene in the absence of rearrangement of the gamma-chain gene. To our knowledge, this has not been previously reported. This finding was unexpected in light of prevailing concepts of T cell ontogeny. Potential explanations for it are discussed.     

The role of Toll-like receptors and related receptors of the innate immune system in asthma

PURPOSE OF REVIEW: The biology of the innate immunity receptors is of central importance in the host response to the environment. Identifying genetic variants that alter the innate immune response is highly relevant to understanding asthma pathogenesis. This review summarizes recent studies of the role of innate immunity receptors, including Toll-like receptors and CD14, in the pathogenesis of asthma. RECENT FINDINGS: The majority of studies published since 2004 have been genetic association studies in various clinical settings, which have found positive associations of single nucleotide polymorphisms in TLR2, TLR4, TLR6 and TLR10 with asthma or atopy, although the number of studies is small and the results not yet replicated. The designs for CD14 genetic studies have been more sophisticated and have included gene-environment interaction. The results of CD14 gene associations with asthma and atopy are suggestive but have not been fully replicated. Potential reasons for non-replication of TLR and CD14 association studies include insufficient power, type I error, population heterogeneity and different phenotypes studied. In addition, there may be differences in CD14 genetic effects between childhood and adulthood, and between levels of endotoxin exposure. SUMMARY: The evidence is still being accumulated for the role of Toll-like receptor polymorphisms in the pathogenesis of asthma. There is emerging evidence for the role of CD14 polymorphisms in the development of asthma and atopy. Further studies of innate immunity in asthma and allergy are required, using rigorous study design, measurement of environmental exposure and intermediate phenotypes to demonstrate single nucleotide polymorphism functionality.     

The role of antigenic peptide in CD4+ T helper phenotype development in a T cell receptor transgenic model

CD4+ Th1 cells play a critical role in the induction of cell-mediated immune responses that are important for the eradication of intracellular pathogens. Peptide-25 is the major Th1 epitope for Ag85B of Mycobacterium tuberculosis and is immunogenic in I-Ab mice. To elucidate the role of the TCR and IFN-gamma/IL-12 signals in Th1 induction, we generated TCR transgenic mice (P25 TCR-Tg) expressing TCR alpha- and beta-chains of Peptide-25-reactive cloned T cells and analyzed Th1 development of CD4+ T cells from P25 TCR-Tg. Naive CD4+ T cells from P25 TCR-Tg differentiate into both Th1 and Th2 cells upon stimulation with anti-CD3. Naive CD4+ T cells from P25 TCR-Tg preferentially develop Th1 cells upon Peptide-25 stimulation in the presence of I-Ab splenic antigen-presenting cells under neutral conditions. In contrast, a mutant of Peptide-25 can induce solely Th2 differentiation. Peptide-25-induced Th1 differentiation is observed even in the presence of anti-IFN-gamma and anti-IL-12. Furthermore, naive CD4+ T cells from STAT1 deficient P25 TCR-Tg also differentiate into Th1 cells upon Peptide-25 stimulation. Moreover, Peptide-25-loaded I-Ab-transfected Chinese hamster ovary cells induce Th1 differentiation of naive CD4+ T cells from P25 TCR-Tg in the absence of IFN-gamma or IL-12. These results imply that interaction between Peptide-25/I-Ab and TCR may primarily influence determination of the fate of naive CD4+ T cells in their differentiation towards the Th1 subset.