Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Compromised immune function is common to Zn deficiency, protein and energy malnutrition; however, the causative mechanisms at the molecular level have not been elucidated. The T lymphocyte signal transduction pathway contains several Zn-finger proteins, and it is possible that the in vivo functioning of these proteins could be affected by dietary deficiency of Zn and amino acids. Thus, the objective was to investigate the effects, on expression of the T lymphocyte signal transduction proteins p56(lck), phospholipase Cgamma1 (PLCgamma1) and protein kinase C (PKCalpha), of dietary Zn deficiency (ZnDF, < 1 mg Zn/kg diet) and protein-energy malnutrition syndromes [2% protein deficiency (LP), combined Zn and 2% protein deficiency (ZnDF+LP), and diet restriction (DR, body weight equal to ZnDF)] compared with control (C) mice. Indices of nutritional status and splenocyte counts were also determined. Based on serum albumin and liver lipid concentrations, the ZnDF+LP and LP groups had protein-type malnutrition, whereas the ZnDF and DR groups had energy-type malnutrition. For Western immunoblotting of the signal transduction proteins, mouse splenic T lymphocytes were isolated by immunocolumns. The expression of T lymphocyte p56(lck) was significantly elevated in the ZnDF+LP, ZnDF and DR groups compared to the C group. In contrast, the expression of PLCgamma1 and PKC was unaffected. There was a significant negative correlation between T lymphocyte p56(lck) expression and serum Zn (r= -0.65, P = 0.0007) or femur Zn (r = -0.73, P = 0.0001) concentrations. We propose that elevated T lymphocyte p56(lck) may contribute to altered thymoctye maturation, apoptosis and lymphopenia in Zn deficiency and protein-energy malnutrition syndromes.
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PMID:Expression of T lymphocyte p56(lck), a zinc-finger signal transduction protein, is elevated by dietary zinc deficiency and diet restriction in mice. 1008 65

TCR and cytokine signals induce naive T cells to undergo spontaneous divisions as part of a homeostatic response to conditions of T cell deficiency. The conditions under which these signals evoke the homeostatic response and their interaction with each other are poorly understood, and yet are very important clinically in considering strategies for immune reconstitution. Here, we show that p56(lck) (lck)-mediated TCR signals and IL-7R signals are each able to stimulate T cell proliferation in lymphopenic hosts independently of one another, but can also synergize to facilitate proliferation. Furthermore, the relative contribution to the homeostatic response by TCR and cytokine signals is not fixed and critically depends on both the degree of lymphopenia and specific characteristics of individual T cell clones. Finally, we show that only lck and not fyn can mediate the TCR-driven proliferation, while neither lck nor fyn is required for IL-7R-induced proliferation.
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PMID:TCR and IL-7 receptor signals can operate independently or synergize to promote lymphopenia-induced expansion of naive T cells. 1224 69

It has been hypothesized that increased expression of the signaling protein p56(lck) disrupts maturation of T lymphocytes, leading to the lymphopenia associated with dietary zinc deficiency and malnutrition. Our objective was to examine p56(lck) protein levels, flow cytometric markers of T cell development (CD4, CD8, TCRalphabeta, TCRgammadelta and CD90) and absolute cell numbers in thymus, spleen and blood of zinc-deficient (ZD), diet-restricted (DR) and control (CTL) rats. Recent thymic emigrant (CD90+) T lymphocytes were also investigated after dietary repletion. P56(lck) protein levels were one- to twofold greater in thymocytes than splenocytes, and ZD rats had more thymocyte p56(lck) protein than CTL rats. In the thymus and blood, the proportions of T lymphocyte subpopulations (CD4-CD8-, CD4+CD8+ and CD4+CD- or CD4-CD8+) were unchanged, except for a higher percentage of TCRalphabeta+CD-CD8+ thymocytes in ZD rats. The 15-29% fewer CD90+ T cells in the blood and spleen of ZD rats were reversed after dietary repletion for 7 and 23 d, respectively. In summary, T-cell numbers were proportional to thymus and spleen weights and unaltered per unit blood volume, despite elevated thymocyte p56(lck) protein in ZD rats. In zinc deficiency, the decreased percentages of CD90+ cells in the blood and spleen could adversely affect the T-cell repertoire.
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PMID:Zinc-deficient rats have fewer recent thymic emigrant (CD90+) T lymphocytes in spleen and blood. 1465 78

Infection by human immunodeficiency virus type 1 (HIV-1) is associated with decreases in peripheral CD4(+) T cells and development of lymphadenopathy. The precise mechanisms by which HIV-1 induces these changes have not been elucidated. T-cell trafficking through lymphoid tissues is facilitated by CCL21-mediated entry and sphingosine-1-phosphate (S1P)-mediated egress. Having previously determined that HIV-1 envelop glycoprotein, gp120, directly alters T-cell migration, we investigated whether gp120 without HIV-1 infection could influence the responses of CD4(+) T cells to the signals involved in T-cell trafficking through lymph tissue. Incubation of normal human T cells with gp120 for 1 h resulted in reprogramming of CD4 T-cell migratory responses by increasing sensitivity to CCL20 and CCL21 and complete inhibition of migration to S1P. Incubation of human T cells with gp120 prior to injection into NOD.CB17-Prkdc(scid)/J mice resulted in increases in lymph node accumulation of CD4(+) T cells, with reciprocal decreases in blood and spleen compared to T cells not exposed to gp120. The effects of gp120 required CD4 signaling mediated through p56(lck). These findings suggest that gp120 alone can alter CD4(+) influx and efflux from lymph nodes in a fashion consistent with the development of lymphopenia and lymphadenopathy.
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PMID:Human immunodeficiency virus type 1 gp120 reprogramming of CD4+ T-cell migration provides a mechanism for lymphadenopathy. 1929 93

Zinc deficiency is one of the leading risk factors for developing disease and yet we do not have a clear understanding of the mechanisms behind the increased susceptibility to infection. This review will examine the interrelationships among the hypothalamus-pituitary-adrenal stress axis, p56(lck), and T-cell maturation in both zinc deficiency and responses during zinc repletion. We will highlight differences between the adult mouse model (wasting malnutrition) and growing rat model (stunting malnutrition) of dietary zinc deficiency and discuss the use of various controls to separate out the effects of zinc deficiency from the associated malnutrition. Elevated serum corticosterone in both zinc deficient and pair-fed rats does not support the hypothesis that zinc deficiency per se leads to corticosterone-induced apoptosis and lymphopenia. In fact, the zinc deficient rat does not have lymphopenia. Thymocytes from zinc deficient mice and rats have elevated levels of p56(lck), a signalling protein with a zinc clasp structure, but this does not appear to affect thymocyte maturation. However, post-thymic T-cell maturation appears to be altered based on the lower proportion of splenic late thymic emigrants in zinc deficient rats. Fewer new T-cells in the periphery could adversely affect the T-cell repertoire and contribute to immunodeficiency in zinc deficiency.
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PMID:Dietary zinc deficiency in rodents: effects on T-cell development, maturation and phenotypes. 2282 46