Lymphoid differentiation

Myers, D. E., Irvin, J. D., Smith, R. S., Kuebelbeck, V. M., and Uckun, F. M. (1991) Production of a pokeweed antiviral protein (PAP)-containing immunotoxin, B43-PAP, directed against the CD19 human B lineage lymphoid differentiation antigen in highly purified form for human clinical trials. J. Immunol. Methods 136, 221-237. 

Axre RBACH, R. (1961b). Genetic control of thymus lymphoid differentiation. Proc. Natl. Acad. Sci. U.S. 47,1175-1181. 

One component of the age-ielated decline in immune function is decreased production of the lymphokine that promotes the growth of T-ceUs, interleukin 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-ceU differentiation has been reported in human cells from elderly 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 weU-known IL-2 inducer. Recombinant IL-2 adrninistered 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). 

In the specialized environment of secondary lymphoid tissues such as lymph nodes or spleen, dendritic cells provide the requirements for naive T-lymphocytes to become activated and to proliferate. The professional antigen-presenting cells present peptides in MHC II, express costimulatory molecules, and release cytokines into the immunological synapse, which is formed by the antigen-presenting cell and the naive T-lymphocyte. Thus, cells of innate immunity initiate and facilitate the activation of naive lymphocytes, and it is easily conceivable that their cytokines and adhesion molecules will instruct the naive T-lymphocyte during activation and differentiation to T-effector cells. 

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... 

Carramolino L, Zaballos A, Kremer L, et al. Expression of CCR9 beta-chemokine receptor is modulated in thymocyte differentiation and is selectively maintained in CD8(+) T cells from secondary lymphoid organs. Blood 2001 97(4) 850-857. 

Karlsson I, Grivel JC, Chen SS, et al. Differential pathogenesis of primary CCR5-using human immunodeficiency virus type 1 isolates in ex vivo human lymphoid tissue. J Virol 2005 79(17) 11151-11160. 

Leonard, W. and Spolski, R. 2005. Interleukin 21 a modulator of lymphoid proliferation, apoptosis and differentiation. Nature Reviews Immunology 5(9), 688-698. 

Total and absolute differential leukocyte counts Globulin levels1 and A/G ratios Lymphoid organs / tissues Thymus, spleen (optional lymph nodes)... 

While changes in cell phenotypes have proved useful in some settings to characterize the immunotoxicity of xenobiotics,1 phenotypic analysis alone is often not a sensitive indicator of low dose immunotoxicity for many agents that alter immune function. Xenobiotics that exert selective toxicity on lymphoid and myeloid cells may be discovered through immunophenotypic analysis. However, most agents produce immunotoxicity at doses much lower than those required to produce cytotoxicity or interfere with primary lymphoid organ differentiation. Some of the most potent immunosuppressive chemicals that have been tested, such as cyclosporine A, do not alter immunophenotype at doses that are immunosuppressive. On the other hand, when phenotyping is linked to assessment of functional parameters of the cells, immunotoxic effects are more likely to be identified. 

There are literally hundreds of markers that are currently available for the mouse and human than can be used to characterize lymphoid and myeloid cells and subsets in primary and secondary lymphoid organs. Many of the markers expressed in mammals are highly conserved across species and have been designated as genetic clusters of differentiation (CD). CDs can be identified with fluorescently labeled monoclonal antibodies. As presented previously, when combined with other fluorescent probes, important information on intracellular biochemistry and cell function can be obtained. Many of the biochemical markers used by immunotoxicologists are common to other... 

Cells of the T cell lineage appear to be more sensitive to the immunomodulatory effects of Pb compared to other lymphoid populations. In addition, there are considerable differences in sensitivity across various T cell subpopulations [38 41], This differential sensitivity has become another major hallmark of Pb-induced immunotoxicity, although most data implicate T cells as indirect targets of Pb immunotoxicity. Both in vivo and in vitro observations of T-dependent immune responses in the presence of Pb suggest that T helper function and Th-dependent cytokines are skewed preferentially toward Th2 reactivities. Smith and Lawrence [42] found that Pb inhibited antigen presentation and stimulated a T cell clone of the Thl phenotype. McCabe and Lawrence [38] were the first to show that Pb inhibited Thl stimulation while it promoted presentation to Th2 clones. Heo and colleagues [39 41] provided both in vitro and in vivo results supporting this immunomodulation by Pb. 

Tabo, J.D. and Paul, W.E. (1973). Functional heterogeneity of murine lymphoid cells. III. Differential responsiveness of T cells to phytohemagglutinin and concanavalin A for T cell subsets. J. Immunol. 110 362-369. 

Lymphocytes are derived from stem cells that differentiate within the primary lymphoid organs (bone marrow and thymus), where they mediate the immune... 

---