CD4+ lymphocytes

Kotler, D. P., Wolinsky, S. M., and Koup, R. A. (1996). Relative resistance to HIV-1 infection of CD4 lymphocytes from persons who remain uninfected despite multiple high-risk sexual exposures. Nature Medicine 2 412-417. 

Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, Markowitz M (1995) Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 373 123-126... 

Two clinical studies with CD4+ lymphocytes expressing an antiviral were performed. Marking in both studies was low but there was some indication for a possible selective advantage conferred by the ribozyme (Buchschacher and Wong-Staal 2001 Macpherson et al. 2005). 

The intestinal mucosa of patients with CD has a preponderance of CD4-+- type 1 helper T cells, while patients with UC have more CD4+ lymphocytes with atypical type 2 helper T cells.9 Likewise, drugs such as non-steroidal anti-inflammatory drugs (NSAIDs) that disrupt the integrity of the GI mucosa may facilitate mucosal entry of intestinal antigens and lead to disease flares in patients with IBD.11... 

Oropharyngeal candidiasis remains the most common opportunistic infection in patients with HIV. Eighty to ninety percent of HIV-positive patients develop oropharyngeal candidiasis.27 For 70% of these patients, it is the first manifestation of HIV infection.28 The incidence of oropharyngeal infection increases with decreasing CD4 lymphocyte counts, with an incidence of 60% in patients with a CD4 count less than 200 cells/mm3. 

The acquired immune deficiency syndrome (AIDS) was first recognized in 1981, and described in a cohort of young homosexual men with significant immune deficiency. Since then, human immunodeficiency virus type 1 (HIV-1) has been clearly identified as the major cause of AIDS.1 HIV-2 is much less prevalent than HIV-1, but also causes AIDS. HIV primarily targets CD4+ lymphocytes, which are critical to proper immune system function. If left untreated, patients experience a prolonged asymptomatic period followed by rapid, progressive immunodeficiency. Therefore, most complications experienced by patients with AIDS involve opportunistic infections and cancers. 

The success of antiretroviral therapy is measured by the degree to which the therapy (1) restores and preserves immunologic function, (2) maximally and durably suppresses HIV RNA, (3) improves quality of life, and (4) reduces HIV-related morbidity and mortality. The major outcome parameters are CD4+ lymphocyte absolute count and percentage, and plasma HIV RNA. Adequate immunologic response in antiretroviral-naive patients consists of an increase in CD4+ cell count that averages 100 to 150 cells/mm3 per year (with a faster response in the first 3 months), and a 1 log decrease in HIV RNA by 2 to 8 weeks after starting... 

GAl-derived proteins were detected in ES products from adult worms and host abomasal mucus, indicative of release from the microvillar surface. Following from this, protective immunity stimulated by immunization with these proteins may involve anamnestic and mucosal immune responses. This suggestion was supported in a later study (Karanu et al., 1997a), which provided evidence for a contribution from CD4+ lymphocytes to gut antigen-induced immunity. 

In brief, EAE can be induced by immunization with several encephalitogenic proteins from myelin, most notably MBP, PLP and myelin-oligodendrocyte glycoprotein (MOG). MBP was the first protein shown to cause EAE, and this classical form of the disease is mediated primarily by CD4+, MHC class II restricted T cells, because it can be transferred from an immunized animal to a naive animal using these cells. These data document the importance of CD4+ lymphocytes for EAE induction, but additional pathogenic roles for other T cell populations are possible, especially in later stages of the disease. Also, there is... 

High viral load (exceeding 50,000 copies/mL in the adult or 500,000 copies/mL in the child) Persistent decrease in CD4 lymphocytes... 

The number of CD4 lymphocytes in the blood is a surrogate marker of disease progression. The normal adult CD4 lymphocyte count ranges between 500 and 1,600 cclls/pb, or 40% to 70% of all lymphocytes. 

The central goal of antiretroviral therapy is to decease morbidity and mortality through maximum suppression of HIV replication (HIV RNA level that is undetectable). Secondary goals include an increase in CD4 lymphocytes. 

Treatment is recommended for all HIV-infected persons with an AIDS-defming event, symptomatic disease, or a CD4 lymphocyte count below 200 cells/mm3 should be offered therapy. Treatment is generally not recommended in persons with CD4 counts above 350 cells/mm3. Those between 201 and 350 cells/mm3 should be offered therapy (Table 40-4). 

The development of certain opportunistic infections is directly or indirectly related to the level of CD4 lymphocytes. 

Currently, PCP prophylaxis is recommended for all HIV-infected individuals who have already had previous PCP. Prophylaxis is also recommended for all HIV-infected persons who have a CD4 lymphocyte count of less than 200 cells/mm3 (i.e., their CD4 cells are less than 20% of total lymphocytes) or a history of oropharyngeal candidiasis. 

Successful containment of M. tuberculosis requires activation of a subset of CD4 lymphocytes, referred to as Th-1 cells, which activate macrophages through secretion of interferon y. 

Gaudy AA, Reddy ST, Chatila T, Atkinson JP, Verbsky JW CD25 deficiency causes an immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like syndrome, and defective IL-10 expression from CD4 lymphocytes. J Allergy Chn Immunol 2007 119 482-487. 

Jutel M, Zak-Nejmark T, Wrzyyszcz M, Malolepszy J Histamine receptor expression on peripheral blood CD4 + lymphocytes is influenced by ultrarush bee venom immunotherapy. Allergy 1997 52(suppl37) 88. 

Figure 17.48 Sequential changes in the number of CD4+ lymphocytes and clinical signs and symptoms of AIDS. The dashed line represents the number of CD4+ lymphocytes the solid line represents the number of virus particles. The timing of the changes is approximate. (Adapted from Rang et at (2000).)...

Tuberculin skin testing is an important part of the care of all HIV-1-infected patients or persons at risk for HIV-1 infection. Tuberculin skin testing should be done using the Mantoux method. A tuberculin reaction of >5 mm of induration is classified as positive in persons known to have or suspected of having HIV-1 infection. Unfortunately, as the CD4 lymphocyte count declines with progression of HIV-1 disease, many patients no longer react to delayed-type hypersensitivity testing. More than 60% of persons with CD4 lymphocyte counts of <200 cells/pl may have skin test reactions of <5 mm. Thus, it is impossible to detect the presence of tuberculous infection in many HIV-l-infected individuals. 

Several pools of nonreplicating virus serve as reservoirs of infection and hmit the effectiveness of antiretroviral therapy. HIV can hve and multiply in monocytes and macrophages these cells are present in all tissues and can live for many months. Infective virus can also reside in long-lived resting CD4+ lymphocytes. 

CBC, metabolic panel, hepatic function panel, CD4 lymphocyte count, HIV RNA level... 

Quang-Cantagrel ND, Wallace MS, Ashar N Mathews C (2001). Long-term methadone treatment effect on CD4+ lymphocyte counts and HIV-1 plasma RNA level in patients with HIV infection. European Journal of Pain, 5, 415-20... 

Success in treating AIDS may depend upon better understanding of the complex life cycle of HIV-1,722,730,735 w -,jc -, js summarized in Fig. 28-27. The cycle begins with the binding of the virion envelope protein to the immunoglobulin-like surface protein CD4, which is found principally on the type T4 helper T cells (Chapter 31). Binding of CD4 to the HIV envelope proteins appears to activate the T cells to enter the cell cycle and to take up and integrate the virus. The virus infection destroys these CD4+ lymphocytes with a half-life of less than two days.735... 

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.

IFN-y is produced by THi cells and shifts the response toward a THi phenotype. This is accomplished by activation of NK cells that promotes innate immunity, augmenting specific cytolytic response and induction of macrophages. The induction of cytotoxic immunity can be direct or indirect via suppression of TH2 response. Another direct effect of IFN-y is the differentiation of naive CD4+ lymphocytes toward a THi phenotype. The cytokines present are very important in this differentiation process. Furthermore, induction of IL-12 and suppression of IL-4 by IFN result in differentiation toward a THi phenotype. 

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