Cell differentiation lymphoid

PAMPs and various tissue factors can prime DCs to produce T-cell-polarizing factors [21], IL-12 is a pro-inflammatory cytokine that induces IFN-y and promotes the development of Thl-cell differentiation [31], Other Thl-polarizing factors are IFN-a and IFN-(3 [32] and cell-surface expressed intracellular adhesion molecule (ICAM)-l [33]. On the other hand, it has been shown that NF-kB inducing kinase (NIK), which is known to regulate B-cell maturation and lymphoid organogenesis, is important for the induction of Thl7 cells [34],... 

FIGURE 90-2. Pathway of normal B-cell differentiation and relationship to B-cell lymphocytes. (Reproduced from Armitage JO, Longo DL. Malignancies in lymphoid cells. In Kasper DL, Braunwald E, Fauci AS, et al, (eds.) Harrison s Principles of Internal Medicine. 16th ed. New York McGraw-Hill 2005 544.)... 

Hematopoiesis is defined as the development and maturation of blood cells and their precursors. In utero, hematopoiesis may occur in the liver, spleen, and bone marrow. However, after birth, it occurs exclusively in the bone marrow. All blood cells are generated from a common hematopoietic precursor, or stem cell. These stem cells are self-renewing and pluripotent and thus are able to commit to any one of the different lines of maturation that give rise to platelet-producing megakaryocytes, lymphoid, erythroid, and myeloid cells. The myeloid cell line produces monocytes, basophils, neutrophils, and eosinophils, whereas the lymphoid stem cell differentiates to form circulating B and T lymphocytes. In contrast to the ordered development of normal cells, the development of leukemia seems to represent an arrest in differentiation at an early phase in the continuum of stem cell to mature cell.1... 

T cell development, similar to B cell ontogeny, can also be divided into stages based on antigen expression (Table 4) extrathymic precursor, prothymocyte, immature thymocyte, common thymocyte, mature thymocyte, and mature peripheral T cell. However, while the early stages of T cell development are well characterized, the later stages of T cell differentiation, that is, those of the mature peripheral T cell, have not been fully delineated (C3, F12, H13, K15, K16, K20, R6-R8,V3, V4). Furthermore, although natural killer (NK) cells are closely related to T cells (S21), the stages of differentiation of this lymphoid cell population are not completely understood. 

CD33 was first identified as a 67 kD differentiation marker for subsets of myeloid cells. It has also been useful as a marker for myeloid versus lymphoid leukemias. CD33 expression in cells of hematopoietic origin has led to the proposal that it participates in myeloid cell differentiation and mediates cellular interactions [240]. 

A basic understanding of normal hematopoiesis is needed before one can understand the pathogenesis of leukemia. The reader is referred to Chap. 98 for a detailed discussion of hematopoiesis. Normal hematopoiesis consists of multiple well-orchestrated steps of cellular development. A pool of pluripotent stem cells undergoes differentiation, proliferation, and maturation, to form the mature blood cells seen in the peripheral circulation. These pluripotent stem cells initially differentiate to form two distinct stem cell pools. The myeloid stem cell gives rise to six types of blood cells (erythrocytes, platelets, monocytes, basophils, neutrophils, and eosinophils), while the lymphoid stem cell differentiates to form circulating B and T lymphocytes. Leukemia may develop at any stage and within any cell line. 

Felgar RE, Macon WR, Kinney MC, et al. TIA-1 expression in lymphoid neoplasms. Identification of subsets with cytotoxic T lymphocyte or natural killer cell differentiation. Am J Pathol. 1997 150 1893-1900. 

One component of the age-related decline in immune function is decreased production of the lymphokine that promotes the growth of T-ceUs, intedeukin 2 (IL-2). Administration of recombinant-derived IL-2, both in vitro and in vivo, appears to restore certain immune functions in aged mice. Recovery of T-regulatory effects on B-cell differentiation has been reported in human cells from eldedy patients treated with IL-1 and/or IL-2 (42). Similar effects have been observed in the presence of the pentapeptide thymopentin [69558-55-0] (Arg Lys Asp Val Tyr), a well-known IL-2 inducer. Recombinant IL-2 administered to aged mice for three weeks has been shown to correct the T-ceU functional deficiency associated with antigen-specific immunoglobulin production by certain lymphoid tissue (43). 

B cell differentiation is a highly regulated process with pathways and steps that have been well delineated (Hardy and Hayakawa, 2001 Rolink et al, 2001). This development depends on intrinsic as well as extrinsic factors. These latter factors mainly originate Ifom interactions of differentiating progenitor B cells with supportive stromal cells. In particular, chemokines, as well as their receptors, play important roles in lymphopoiesis and in lymphoid organ development (Ansel and Cyster, 2001 Parkin and Cohen,... 

Table 5 compares DNA strand breaks and their repair in different lymphoid tissues. It is interesting that thymocytes contain fewer breaks than splenocytes and do not imdergo further decrease in number of breaks after stimulation with Con A plus interleukin 2 (IL-2). This may give some support to the hypothesis that DNA strand breaks are associated with cell differentiation. Most of the cells in the thymus are immature and not yet fully differentiated [18] they may not yet have acquired the breaks observed in splenocytes. Nevertheless, MBA inhibited th3miocyte proliferation and also caused an accumulation of strand breaks proportional to the duration of incubation of inhibitor (Fig. 1), as in the case of splenocytes. This also suggests that... 

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