Lymphocyte accumulation

Burman A, Haworth O, Hardie DL, et al. A chemokine-dependent stromal induction mechanism for aberrant lymphocyte accumulation and compromised lymphatic return in rheumatoid arthritis. J Immunol 2005 174(3) 1693-1700. 

As with the increase in phosphomonoester signal, these changes in the spectra of lipids are not necessarily indicative of a malignant cell. For example, mitogen-stimulated lymphocytes accumulate cytoplasmic lipid droplets (Tanaka et al., 1963) and show the high resolution H lipid signals (Mountford et al., 1982). 

Comparable findings have been noted in experimental bronchitis produced in rats exposed by inhalation to sulfur dioxide ( ). In that setting, the progression of the pathology is noxious inhalant, inflammatory cellular response, hypersecretion, and lastly, lymphocytic accumulations with or without bacterial pneumonitis. Comparable studies in man do not exist. Consequently there is still controversy relative to the initial pathology in human bronchitis which must occur at a stage before it can be called "chronic". 

Metal ions released from metal implants by osteoclastic bio-corrosion are distributed through- out the body and are eventually taken up by dendritic cells, the most potent anti-gen-presenting cells [14, 15, 18]. Besides changing phenotypic and functional properties of dendritic cells [18], metal ions complex with cellular proteins and peptides. In case of titanium, the ions form complexes with phosphorus-containing proteins and peptides (usually signaling molecules), nucleotides (DNA in the nuclease and RNA in the cytoplasm) and lipids (phospholipids of the cellular membranes) [15]. The new antigenic metal-peptides are presented by dendritic cells to specific T-lymphocytes that react and are activated [15]. The dendritic cells and activated T-lymphocytes accumulate in tissues with high metal concentrations, usually close to the metal implant, and form inflammatory reactions [7] that include secretion of inflammatory cytokines, such as TNF-a, TGF-b, interleukin-6 and interleukin-lb [19]. Most important is secretion of RANK-L by the activated T-lymphocytes, an essential factor for maturation, survival and function of osteoclasts [19]. 

The consequence of ADA deficiency is accumulation of adenosine and 2 -deoxyadenosine, substances toxic to lymphocytes, important cells in the immune response. 2 -Deoxyadenosine is particularly toxic because its presence leads to accumulation of its nucleotide form, dATP, an essential substrate in DNA synthesis. Elevated levels of dATP actually block DNA replication and cell division by inhibiting synthesis of the other deoxynncleoside 5 -triphosphates (see Chapter 27). Accumulation of dATP also leads to selective depletion of cellular ATP, robbing cells of energy. Children with ADA SCID fail to develop normal immune responses and are susceptible to fatal infections, unless kept in protective isolation. 

Pentostatin (deoxycoformycin Fig. 4) is a purine isolated from cultures of Streptomyces antibioticus. Its mode of action involves inhibition of adenosine deaminase, which plays a key role in purine salvage pathways and DNA synthesis. As a consequence, deoxyadenosine triphosphate (dATP) is accumulated, which is highly toxic to lymphocytes. This is associated with augmented susceptibility to apoptosis, particularly in T cells. 

Adenosine deaminase deficiency is associated with an immunodeficiency disease in which both thymus-derived lymphocytes (T cells) and bone marrow-derived lymphocytes (B cells) are sparse and dysfunctional. Purine nucleoside phosphorylase deficiency is associated with a severe deficiency of T cells but apparently normal B cell function. Immune dysfunctions appear to result from accumulation of dGTP and dATP, which inhibit ribonucleotide reductase and thereby deplete cells of DNA precursors. 

At cellular level each stage of atheroma development is accompanied by the expression of specific glycoproteins by endothelial cells which mediate the adhesion of monocytes and T-lymphocytes. Their recruitment and migration is triggered by various cytokines released by leukocytes and possibly by smooth muscle cells. Atheroma development continues with the activation of macrophages, which accumulate lipids and become, together with lymphocytes, so-called fatty streaks. The continuous influx, differentiation and proliferation finally leads to more advanced lesion and to the formation of the fibrous plaque. ... 

CLL is a cancer that results in the accumulation of functionally incompetent lymphocytes.15 CLL is considered an indolent, incurable disease in which treatment should be initiated when patients have symptoms. However, some patients have aggressive disease and need to be treated with intensive therapy. 

CLL is characterized by small, relatively incompetent B lymphocytes that accumulate in the blood and bone marrow over time. The exact cell of origin is controversial but has been described as an antigen-activated B lymphocyte.3... 

Induction of expression of various adhesion molecules on the surface of vascular endothelial cells. These act as docking sites for neutrophils, monocytes and lymphocytes, facilitating their accumulation at local sites of inflammation. 

The function of the ALD protein is not fully understood, and knockout mice lacking it do not exhibit the severe CNS neurological deficits commonly associated with the human disease despite a similar accumulation of VLCFAs [26], Furthermore, the clinical variability in human patients cannot be accounted for by the severity of the biochemical abnormality or the nature of the gene defect. These observations, plus other data from mice with defects in VLCFA metabolism, raise the issue of whether the accumulation of VLCFAs in myelin is crucial to the pathological mechanisms or is an epiphenomenon. Unlike most other lipid-storage diseases, active ALD brain lesions are characterized by perivascular accumulation of lymphocytes. For this reason, it has been hypothesized that the severity of CNS pathology may relate to an autoimmune reaction that varies from patient to patient and... 

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