CD4 positive cells

The family of apelin peptides is derived from a single gene, activate a single G-protein-coupled receptor and are substrates for the angiotensin converting enzyme-2 (ACE2). Apelins regulate cardiovascular function and fluid homeostasis. The apelin receptor also functions as a co-receptor for infection of CD4-positive cells by human immunodeficiency vims ( HIV). 

Figure 5. Formation of multinucleated giant cell from HIV-infected cell and CD4-positive cell.

Hudarabine phosphate is a fluorinated nucleotide analog of the antiviral agent vidarabine. Its cytotoxicity is not well understood. It is rapidly dephospho-rylated at the cell membrane level and then rephos-phorylated intracellularly by deoxycytidine kinase to the active triphosphate derivative. It inhibits DNA polymerase and DNA primase. It is also incorporated into DNA and RNA. Hudarabine is administered intravenously by infusion over 30-120 min. It is eliminated by renal excretion with a terminal half life 10 hours. Adverse effects include myelosuppres-sion, nausea, vomiting, chills and fever. The number of CD4 positive cells is reduced and the incidence of opportunistic infections is increased. 

Anti-thymocyte globulin (ATG) is a purified immunoglobulin from horse, rabbit, sheep, or goat serum after immunization with human thymocytes. The administration of anti-thymocyte globulin results in a depletion of T-cells as a result of complement dependent lysis and opsonization by the macrophage-monocyte system. The depletion of CD4 positive cells is long lasting and results in an inversion of the CD4/CD8 ratio. There are hardly... 

Fig. (12). Augmented expression of CD18, CD25, CD54, CD69 and CD71 in CD4 positive cells in regional lymph nodes following CVS injection on day 9 upon tumor rechallenge [44]. See legend to Fig. (10).

Fig. 3. Three-color analysis of peripheral blood lymphocytes for CD45RA, CD45RO, and CD4. Lymphocytes were stained with antibodies directly labeled with FITC, PE, and PECy5, respectively. The distribution of control labeled cells is shown in A and B, and labeled cells in C—F. The relationship between CD45RA and CD45RO in CD4-positive cells is shown in (F), which is gated for PECy5-positive cells.

Bishop DK, Shelby J, Eichwald EJ. 1992. Mobilization of T lymphocytes following cardiac transplantation. Evidence that CD4- positive cells are required for cytotoxic T lymphocyte activation, inflammatory endothelial development, graft infiltration and acute allograft rejection. Transplantation. 53 849-857. 

Bishop DK, Li W, Chan SY, Ensley RD, et al. 1994. Helper T lymphocytes unresponsiveness to cardiac allografts following transient depletion of CD4-positive cells. Implications for cellular and humoral responses. Transplantation. 58 576-584. 

Another condition that involves analysis of peripheral blood leukocytes is AIDS. Early in the natural history of the disease (or at least in the natural history of immunologists awareness of the disease), it was discovered that one subpopulation of T lymphocytes in particular was destroyed by the HIV virus the cells destroyed are those that possess the CD4 protein on their surface. It is this CD4 protein that appears to be a receptor involved in virus targeting. Therefore, much of the diagnosis and staging of AIDS involves the enumeration of CD4-positive cells in the peripheral blood (Fig. 10.4). 

These techniques—for counting CD4-positive cells in connection with AIDS diagnosis and for phenotyping various populations of... 

Although T cells can be divided into two populations (helper/inducer and cytotoxic/suppressor) based on CD4 and CD8 expression, T cells can also be divided into two populations based on the structure of the antigen receptor complex, either alp, or yIS, associated with the CD3 antigen (DIO). The yIS T cells represent approximately 5% of all T cells, lack expression of CD5, CD4, and often CD8, are thought to be associated with a more primitive type of immune response, and are usually found in the splenic red pulp and epithelial sites (A15, C26, T6). The alj3 T cells usually express all four pan-T cell antigens (CD2, CD3, CD5, and CD7) and either CD4 or CD8. The CD4-positive cells can be further divided based on cytokine secretion Thl cells, which secrete interleukin-2 (IL-2) and interferon y and help macrophages and other T cells, and Th2 cells, which secrete IL-4, IL-5, IL-6, and IL-10 and help B cells in antibody production (DIO, Dll). 

Isolation of CD4 Positive Cells by Magnetic Cell Sorting... 

Determine the percentage of CD4-positive cells by staining with FITC-Leu3a and FACS. 

Repeat steps 1-9 until no further enrichment of CD4-positive cells is obtained. 

Wash the CD4-positive cells with PBS twice at room temperature and suspend the cells at 5 x 106 cells per mL of PBS. 

Farzan, M., Choe, H Martin, K Marcon, L., Hofmann, W Karlsson, G., et al. (1997) Two orphan seven-transmembrane segment receptors which are expressed in CD4-positive cells support simian immunodeficiency virus infection.. /. Exp. Med. 186,405 411. 

The majority of small lymphocytes in early MS lesions and in the hypercellular edge of plaques extending into normal white matter are CD4-positive T lymphocytes.108110 T lymphocytes of the CD8 phenotype are present in early lesions but this population predominates in later lesions.111 Examination of the distribution of T-lymphocyte subsets in MS plaques of different activity has led to the proposal that CD4-positive cells are responsible for the development and expansion of lesions, whilst the CD8-positive subset controls their local activity.110112... 

Over a period of time, these CD4-positive T-cells are destroyed, as much by the activated killer T-cells as by the virus itself, and the loss of these cells is evidenced by the lowering of the numbers of detectable CD4-positive cells. These should normally number around 800-1200 per cubic millimetre of blood, but this count drops initially to around 500 in HIV-positive patients and then to less than 200 in patients with full-blown AIDS. This process may take a few years, but typically takes around 10 years. 

Subacute sclerosing panencephalitis and milder encephalitis are caused by measles virus. Focal lymphocytic inflammation in the leptomeninges and perivascular spaces, with many CD4-positive cells, patchy GFAP-positive fibrillary astrocytosis, and occasional microglial nodules, involves the cerebral cortex. Diffuse mononuclear inflammation, gliosis, and loss of myelin occur in subcortical white matter. Inclusion bodies are Cowdry type A and may be seen on H E-stained slides their specific identification requires IHC. °... 

HIV-1 invades and destroys the CD4 positive cells of the immune system. Like other retroviruses, the life cycle requires incorporation of viral genetic material into the host genome. Subsequent transcription and translation events generate virus progeny. Release of the new virus particles is fatal to the host CD4 positive cell. A gradual depletion of immune cells occurs over a period of years and compromises the immune response to the extent that infections that normally would be relatively benign can become life threatening and deadly. 

Fig. 1. Analysis of resting CD4 T cells purified from peripheral blood. Cells were purified from peripheral blood through antibody-mediated negative depletion. Shown are cells stained with FITC-labeled antihuman CD4 antibody before (a) and after (b) purification. In this example, unpurified blood mononuclear cells contain 31% of CD4-positive cells, and following purification, the CD4-positive cells were enriched to 95.1%.

Clapham, P. R., Blanc, D., and Weiss, R. A. (1991) Specific cell surface requirements for the infection of CD4-positive cells by human immunodeficiency virus types 1 and 2 and by simian immunodeficiency virus. Virology 181, 703-715. 

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