Enhanced HIV-1 replication in Vβ12 T cells due to human cytomegalovirus in monocytes: Evidence for a putative herpesvirus superantigen

Dobrescu, Dana; Ursea, Bogdan; Pope, Melissa; Asch, Adam S.; Posnett, David N.

doi:10.1016/0092-8674(95)90472-7

Cited by 88 publications

(36 citation statements)

References 43 publications

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“…42 This has been proposed in cytomegalovirus infection. 43 However, we were able to provide evidence that in vitro, a CVB3-triggered, superantigen-driven response gave results very similar to those observed in the pathogenic scenario of the cases of IDC studied.…”

Section: Discussionmentioning

confidence: 65%

Idiopathic Dilated Cardiomyopathy

et al. 1998

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Background-Many cases of idiopathic dilated cardiomyopathy (IDC) result from an inflammatory myocarditis. The specific immunological mechanisms are not yet defined. Various autoimmune diseases are associated with superantigentriggered immune responses, resulting in massive T-cell activation and tissue damage. We studied 3 cases in a search for evidence that such a phenomenon is also implicated in IDC. Methods and Results-Myocardial, lymph node, and thymic tissue samples were obtained from IDC patients who were undergoing heart transplantation. Infiltrating immune-cell phenotypes and gene expression of T-cell receptor (TCR) ␣-and ␤-chain variable (V␣ and V␤) regions were analyzed by immunostaining and polymerase chain reaction. Similar technical approaches were used to assay the tissues for the presence of coxsackievirus B (CVB). In all the specimens analyzed, an overexpression of the TCR V␤3, V␤7, and V␤13.1 gene families was detected among the infiltrating T cells. These tissues were also found to be CVB3-positive. In vitro exposure of peripheral blood mononuclear cells to lysates of cells infected with CVB3 was capable of stimulating expansion of the same TCR V␤ families. The TCR V␣ repertoire was never found to be skewed. Conclusions-A superantigen-mediated immune response is involved in human heart disease. CVB3 may directly or indirectly trigger this response, suggesting a possible mechanistic link between CVB infection and myocarditis development progressing to IDC. (Circulation. 1998;98:777-785.)

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Section: Discussionmentioning

confidence: 65%

Idiopathic Dilated Cardiomyopathy

et al. 1998

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“…Previous work has suggested that CMV may encode a T cell superAg for T cells expressing the V␤12 T cell receptor (TCR) ␤-chain (19). Such a superAg could not account for the observed CMV responses in normal individuals as there was no relationship between V␤12-expressing T cells and CMV responses.…”

Section: Establishment Of a Flow Cytometric Assay Of Ag-specific T Cementioning

confidence: 72%

Determination of antigen-specific memory/effector CD4+ T cell frequencies by flow cytometry: evidence for a novel, antigen-specific homeostatic mechanism in HIV-associated immunodeficiency.

Waldrop¹,

Pitcher²,

Peterson³

et al. 1997

J. Clin. Invest.

518

340

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The highly regulated secretion of effector cytokines by CD4 ϩ T cells plays a critical role in immune protection against pathogens such as cytomegalovirus. Here, we directly compare the frequency and functional characteristics of cytomegalovirus-specific CD4 ϩ memory/effector T cells in normal and HIV ϩ subjects using a novel, highly efficient multiparameter flow cytometric assay that detects the rapid intracellular accumulation of cytokine(s) after short-term (6 h) in vitro antigen stimulation. Responses in this assay correlate precisely with independent measures of sensitization history (e.g., seroreactivity), and allow the simultaneous assessment of multiple cytokines in single effector T cells. Healthy HIV Ϫ individuals manifested an average of 0.71, 0.72, 0.38, and 0.06% CD4 ϩ T cells responding to cytomegalovirus with ␥ -IFN, TNF-␣ , IL-2, and IL-4 production, respectively, with the simultaneous production of ␥ -IFN, TNF-␣ , and IL-2 being the most common effector phenotype. Significantly, overall cytomegalovirus-specific CD4 ϩ effector frequencies were markedly higher among 40% of HIV ϩ subjects (2.7-8.0%), and demonstrated a predominately polarized ␥ -IFN ϩ /TNF-␣ϩ /IL-2 Ϫ /IL-4 Ϫ phenotype. In contrast, CD4 ϩ effector frequencies for heterologous, nonubiquitous viruses such as the mumps virus were low or absent in the HIV ϩ group. These data suggest the existence of homeostatic mechanisms in HIV disease that selectively preserve memory T cell populations reactive with ubiquitous pathogens such as cytomegalovirus-likely at the expense of T cell memory to more sporadically encountered infectious agents. ( J. Clin. Invest. 1997. 99:1739-1750.)

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“…Recently it was reported that CMVinfected MO enhanced HIV replication in V␤-12 T cells. This enhancement required direct cell to cell contact and viable virus, and it was mediated via a CMV gene product that possesses a superantigen-driven V␤-12 selective property (36). This may affect the rate of HIV replication and consequently lymphocyte depletion leading to immunosuppression.…”

Section: Discussionmentioning

confidence: 99%