热点，广泛关注、研究
1．The mechanisms governing the homeostasis of memory T cells have been an area of intense investigation.
2．Extensive work has been done in the area of cytokine signaling.
3．Not unexpectedly, the newest ‘lineage’ of helper T cells, TH-17 cells, also received a great deal of attention at the Ringberg meeting.
4. While the interactions of DC with naive T cells within LN have been analysed in detail,…
5. While interactions of DC with naive T cells in LN have been extensively examined by 2P-IVM,
6. Although the signals that control neutrophil migration from the blood to sites of infection have been well characterized, little is known about their migration patterns within lymph nodes or the strategies that neutrophils use to find their local sites of action.
不像B，which…，A…
1. Unlike naive T cells, which survive largely in interphase, memory T cells persist under normal conditions with a slow but constant turnover.
像…一样
1．As with naive T cells, memory T cells are also capable of undergoing more rapid cell division under lymphopenic conditions, known as acute
homeostatic proliferation.
…已有共识
1．There is now a general consensus that two members of the common γ chain cytokine family, namely IL-7 and IL-15, control the homeostasis of CD8+
memory cells
…仍不清楚
1. However, the factors that govern the homeostasis of CD4+ memory cells have yet to be fully defined.
2. Although molecular details of the process are poorly understood.
3. Although why this subset of T cells is uniquely sensitive to IL-2 is currently unclear.
4. experiments directly interrogating the physiological requirements
for DC-produced IL-2 have yet to be published.
5. Among the questions that remain to be resolved are 图片how IL-2 may play both supportive and restrictive roles in the same transgenic OT-1 CD8+ T cells.
6. The cause of this disease has been elusive because the SAP gene is not affected in XLP 2 patients.
7．The main source of IL-17 at the local site of inflammation still remains unknown.
8. Whether such a mechanism is relevant to CD4+ T helper cells remains an open issue.
9. Whether the failure to silence TRAIL synthesis upon rechallenge explains this example of AICD remains to be investigated.
10. Whether the receiving cell must make contact with the producing cell or whether there is a role for soluble IL-15/IL-15Rα complexes in CD8+ memory T cell homeostasis is not clear.
11. But the question of whether they need tonic signals via their TCR is still open.
12. Exactly what CD4+ T cells provide to maintain CD8+ T cell memory remains a mystery.
13． Large questions remain as to how chemokine signaling regulates or is regulated to coordinate the complex in vivo dynamics of the T lymphocytes。
14. However, what has not been delineated is the response of effector T cells at nonlymphoid tissue sites when they reencounter Ag.
15. The precise role of IL-2 in the regulation of CD8 T cell responses to foreign Ag in vivo however remains enigmatic.
16．Our understanding of the developmentalcontrol of V(D)J recombination on the one hand, and that of cell proliferation, death, and survival during differentiationon the other, is still fragmentary.
…已经得到公认
1．It is well accepted that two cytokines, namely IL-7 and IL-15, are involved in maintaining the numbers of CD8 memory cells in vivo (145–147).
与…相似
1．In addition, there is a high-affinity receptor for IL-15, referred to as IL-15Rα, and it was thought, in analogy with the IL-2R, that a three-chain complex, αβγ, was the receptor for IL-15 on NK cells and memory CD8+ T cells.
仍存在争议
1．It was clear that there is no shortage of controversy.
可以肯定地说
1．It is safe to say, in fact, that there is a long way to go before the field fully understands the process of effector and memory cell differentiation, the relationships among these post-activation cell fates and the extent to which any given T cell adopts a fixed versus a flexible functional program after antigen activation.
2. There is no doubt immunological research has been boosted by the
recent application of 2P-IVM
依赖、需要
1．Ag-specifi c memory CD8+ cells, on the other hand, are less dependent on IL-15, relying more on IL-7, but still require IL-15 for basal homeostatic proliferation and long-term maintenance
2．Furthermore, robust CD8 recall responses appear to be particularly reliant on CD8 costimulation via 4-1BB.
A与B之间的差异
1．The discrepancy in the homeostatic requirements for Ag-specifi c memory versus MP cells appears even greater for CD4+ than CD8+ cells.
与…一致,相符
1．Consistent with this notion, recent studies have shown that IL-7 is essential for the survival and basal homeostatic turnover of Ag-specific CD4+memory cells.
2. Similarly broad expression of IL-2 and IL-15 receptors do not coincide well with the highly restricted roles that IL-2 and IL-15 appear to play in thymic development.
3．The distinct functions of IL-2, IL-15, and IL-7 signals in naive T cell homeostasis correspond well with the expression patterns of the various receptor chains.
4. A comparison of wild-type and CD25?/? CD8+ T cells side by side in a mixed radiation chimera following LCMV or Listeria infection revealed that the knockout cells could divide as fast as wild-type cells and accumulate to large numbers of effectors (54), in line with previous findings.
5． These experiments are also in agreement with physiological studies showing that T cells activated by soluble peptide in vivo are not committed to tolerance after 3 d
6. Results presented in this work do not contradict this hypothesis, but suggest that in addition to its function as a “T cell graveyard,” the liver may play a role in primary activation of CD81 T cells specific for Ags presented within the liver, including peptides delivered by the i.v. route.
被迫
1．These effector T cells undergo a dramatic contraction in numbers after antigen clearance, with 90 – 95% succumbing to apoptosis within
weeks.
与…相反,相反地…
1. In contrast to CD8 memory T cells, CD4 memory T cells may not require the signals through common cytokine receptor chain.
2. By contrast, IL-2 signaling may play a major role in the differentiation of regulatory T cells
3. Contrary to T-cell recognition of peptides processed and presented on MHC molecules by DC, immunoglobulin receptors on B cells recognize intact protein antigens in their native state.
参与了
1. The polycomb group (PcG) gene Bmi1 has recently been implicated in the maintenance of hematopoietic…
2. an intrinsic histone H3-K27 methyltransferase activity, which implicates a likely mechanism for PcG-mediated gene silencing.
本课题研究了…在…的作用
1. We herein investigated the role of Bmi1 in the generation and maintenance of memory CD4 + Th1/Th2 cells.
研究(清楚)表明…
1. Our results indicate that Bmi1 controls memory CD4 T cell survival and function through the direct repression of the Noxa gene.
2. However, follow-up studies have not revealed an obvious defect in thymic selection
3. Multiple in vitro studies demonstrate that T cell activation depends on the presence of IL-2.
4. The results conclusively demonstrated that IL-2 was dispensable
as a growth factor for antiviral CD8 T cells in secondary lymphoid
tissues
在…方面缺乏让人信服的证据
1．Compelling evidence in this regard is currently lacking.
与…相比
1. Although the expression levels of IL-7R _ and IL-2R _ were slightly lower on Bmi1 _ / _ memory Th2 cells as compared with wild-type cells.
静脉过继转移到…
1. (A and 图片Bmi1 +/+ , Bmi1 +/ _ , or Bmi1 _ / _ effector Th2 (A) or Th1 (图片 cells with DO11.10 Tg background were intravenously transferred into BALB/c nu/nu mice.
大量的证据表明…
1．Hence, despite a plethora of in vitro evidence showing that IL-2 was critical for supporting T cell activation, the dominant physiological function of IL-2 signals in vivo is to restrain T cell activation and prevent autoimmunity.
A对B很重要
1．IL-2 is clearly essential/critical for Treg differentiation.
2．The non-homologous DNA end-joining (NHEJ) pathway has an essential role in joining double-strand breaks (DSBs) generated by the RAG proteins during V(D)J recombination;
3. CD4+ T cells play an essential role in promoting the initial expansion of CD8+ T cells responding to initial antigen challenge when antigen comes from a relatively noninflammatory immunogen.
4. One attractive possibility is that the subset of endogenously activated CD4+ T cells that express low levels of CD25 and make numerous cytokines are key to maintaining CD8+ memory T cells.
5．DCs are central to the priming of both primary and secondary CD8+ T cell responses.
6. Our results therefore suggest that TLRs can play a crucial role in shaping the development of the adaptive immune system.
引出…问题
1．These results raise the question of the extent to which the suppressive actions of TGF-β and IL-27 are mediated by their capacity to promote IL-10 production by other cells.
2．The observation that CD8+ T cell differentiation is programmed after a relatively short exposure to antigen has brought into question the nature of CD8+ T cell–DC interactions in vivo.
3．The expression of AID in developing B cells in both mutant and normal mice (Maoet al., 2004) raises questions regarding the mechanism of AID induction at these early stages of B cell development.
不奇怪地，可以预期地
1．Not unexpectedly, the newest ‘lineage’ of helper T cells, TH-17 cells, also received a great deal of attention at the Ringberg meeting.
2. As expected, RAG-2 expression is detected only in pre-B and immature B cells, validating our cell-purification procedure.
面对严峻的挑战
1．The question then became how to tackle such a daunting challenge.
除了…以外
1．Aside from CD28, perhaps the best described CD8-specific costimulatory molecule is 4-1BB (CD137).
…观点最近也受到挑战
1．The paradigm that SHM is limited to mature B cells has also been recently challenged by a report showing that…
为了研究…我们…
1. To directly address the role of AID during B cell development, we have now analyzed the expression of AID in the BM of normal mice.
…老鼠是…背景的
1． Because Aicda_/_ mice are on a mixed C57BL/6 and CBA background.
2. These nude mice have a C57BL/6 genetic background
有研究指出
1．Previously, it has been reported that about 16% of C57BL/6 immature B cells express AID by single-cell analysis.
2. A previous report had shown AID expression, but no SHM of light chain, in immature B cells from wild-type C57BL/6 mice (Mao et al., 2004).
3. Previous studies have indicated that B cells expressing rearranged
Vk4 genes are frequently negatively selected, perhaps because they are autoreactive
为了证明…
1. In order to ascertain that AID expressed in pre-B and immature B cells is active and functional, the presence of circle transcripts (CTs) and postswitch transcripts.(PSTs) was assessed in these cells.
2. To confirm that CSR led to proper recombination, we amplified PSTs for
each isotype by using specific primers
为了进一步证实、验证、定量…
1. To further determine whether CSR in developing B cells led to appropriate cell-surface protein expression, we stained BM cells from Aicda+/_ and Aicda_/_ mice and examined the surface expression of IgA by using FACS.
2. To circumvent this potential problem, we performed studies in a model system not requiring infection.
值得注意的是…
1. It is noteworthy that CT-a exhibit two transcripts, because of alternative splicing donor sites in the Ia exon.
2. It is important to note that several observations indicate that small numbers of BM-residing plasma or memory B cells cannot account for our findings of AID expression in early B cells.
暗示
1． This is reminiscent of the genetic background effects we find for CSR in pre-B and immature B cells in normal mice.
我们的研究为…提供证据
1．Our findings provide evidence that the innate immune system plays an important role in shaping adaptive immunity at early stages of lymphocyte development.
特别强调
1．We place special emphasis on what we see as a hierarchical organization of lymphoid tissue in support of the cell–cell interactions underlying adaptive immune responses
仅仅讨论
1．So here we limit our discussion to the practical aspects of these techniques
提示
1．Seminal work on two-photon microscopy from the Cyster group shed light on the central role of chemokines on distinct events in B cell biology.
把…叫做…
1. In this study, we will refer to the former cells as CD11b_ dendritic cells and the latter as CD8_ dendritic cells.
据我们所知
1．To our knowledge, this is the first report demonstrating that naive T cells can undergo primary activation outside lymphoid organs.
综上所述
1．Viewed in toto, these results indicate that T cells activated in the lymph nodes of Met-Kb mice are mostunlikely to have contributed to the blood T cell pool during the first 2 days after transfer.
2．Taken together with our previous in vitro data indicating that CD81 T cells can be directly activated by hepatocytes, but then die by neglect due to a lack of costimulation
3．These observations collectively demonstrate that dysregulated miR-155 can affect myeloid or lymphoid development depending on the context of its expression.
不管
1．Our findings indicated that activated CD8 T cells migrated pervasively to all nonlymphoid organs irrespective of the site of initialAg engagement.
2．However, regardless of the tissue of origin, reactivation of transferred memory cells resulted in widespread dissemination of new effector cells.
浅谈
1．Here we bring together much of this work, which has so far only scratched the surface of this very fertile field of investigation,
使
1．Conditional deletion of Dicer in hematopoietic stem cells (HSCs) renders these cells unable to reconstitute the hematopoietic system,
可以从…得到证明
1．The importance of proper regulation of miR-155 expression is exemplified by its much higher expression in several types of hematopoietic malignancies。
需要进一步的研究…
1．However, further studies are needed to determine the extent to which physiologically regulated miR-155 expression directs hematopoietic cell fate ‘decisions’during infection.
适用于
1．Optical microscopy employing fluorescence techniques is highly suited for this purpose, permitting both labeling of specific cells, organelles, or proteins and functional readout of physiological even...
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