Thymic size on chest radiograph and rapid disease progression in human immunodeficiency virus 1-infected children

Meyers, Alan; Shah, Amrik; Cleveland, Robert H.; Cranley, William R.; Wood, Beverly P.; Sunkle, Susan; Husak, Scott; Cooper, Ellen

doi:10.1097/00006454-200112000-00004

Cited by 21 publications

(12 citation statements)

References 30 publications

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“…Classification of the thymus as small/involuted required visualization of 'the superior vena cava, the main pulmonary artery, the aorta-pulmonary artery window and the anterior junction line on AP view and either the pulmonary artery or anterior aspect of the right ventricle and an empty retrosternal space on the lateral view' [14] . This dichotomous approach (small: yes/no) acknowledges the imprecision that other methods ignore [15] .…”

Section: Radiographic Determination Of Thymus Involutionmentioning

confidence: 99%

Thymus Involution and Cerebral White Matter Damage in Extremely Low Gestational Age Neonates

2006

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Background: Among newborns who die, those who have cerebral white matter damage are more likely than others to have thymus involution and low thymus weights. Objective: We sought to evaluate in a population of preterm newborns who did not die if those who developed a cerebral white matter damage (as defined by an echolucency) are more likely than others to have thymus involution as assessed on chest radiographs. Method: The 89 infants whose data were evaluated were born before the 28th week of gestation, had at least one chest radiograph within the first 2 days of life (to determine thymus size), and at least one cranial ultrasonogram to assess for white matter echolucency. Results: Eighty-five percent of these infants had a small thymus within the first 2 weeks of life. Median time to thymus involution in those born before the 26th week of gestation was 36 h, and in those born during or after the 26th week of gestation was 140 h. Infants who developed involution before the median time in their respective gestational age groups were classified as early involuters (group 1) and were compared to their peers with late/no involution (group 2). Infants with an echolucency were more likely to have had early involution than infants without an echolucency (89% vs. 44%) (p = 0.01). This relationship was not distorted by potential confounders. The echolucency odds ratio associated with early thymus involution was consistently above 8 in all strata of the sample. Conclusion: These results are consistent with the possibility that early thymus involution and neonatal white matter damage are not independent phenomena and may have common antecedents.

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Section: Radiographic Determination Of Thymus Involutionmentioning

confidence: 99%

Thymus Involution and Cerebral White Matter Damage in Extremely Low Gestational Age Neonates

2006

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“…This interpretation is supported by a series of published data. Children whose thymuses are infected progress rapidly towards AIDS (8,26,35,38). This might be sometimes related to the fact that in infants infected by their seropositive mothers (50).…”

Section: ͻ10mentioning

confidence: 99%

“…Thymuses from pediatric patients undergoing an accelerated disease process (8,26,35,38) or from adults with AIDS (14,48) show severe thymocyte depletion associated with a profound disorganization of the thymic epithelial network. Thymic failure may also be responsible for the fact that, among patients undergoing antiretroviral therapies for advanced disease, the CD4 cell counts often remain below normal levels despite long-term suppression of viral load (32,62).…”

mentioning

confidence: 99%

Positive Regulation of CXCR4 Expression and Signaling by Interleukin-7 in CD4⁺Mature Thymocytes Correlates with Their Capacity To Favor Human Immunodeficiency X4 Virus Replication

Schmitt

Chêne

Boutolleau

et al. 2003

J Virol

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The emergence of X4 human immunodeficiency virus type 1 (HIV-1) variants in infected individuals is associated with poor prognosis. One of the possible causes of this emergence might be the selection of X4 variants in some specific tissue compartment. We demonstrate that the thymic microenvironment favors the replication of X4 variants by positively modulating the expression and signaling of CXCR4 in mature CD4 ؉ CD8؊ CD3 ؉ thymocytes. Here, we show that the interaction of thymic epithelial cells (TEC) with these thymocytes in culture induces an upregulation of CXCR4 expression. The cytokine secreted by TEC, interleukin-7 (IL-7), increases cell surface expression of CXCR4 and efficiently overcomes the downregulation induced by SDF-1␣, also produced by TEC. IL-7 also potentiates CXCR4 signaling, leading to actin polymerization, a process necessary for virus entry. In contrast, in intermediate CD4 ؉ CD8 ؊ CD3 ؊ thymocytes, the other subpopulation known to allow virus replication, TEC or IL-7 has little or no effect on CXCR4 expression and signaling. CCR5 is expressed at similarly low levels in the two thymocyte subpopulations, and neither its expression nor its signaling was modified by the cytokines tested. This positive regulation of CXCR4 by IL-7 in mature CD4؉ thymocytes correlates with their high capacity to favor X4 virus replication compared with intermediate thymocytes or peripheral blood mononuclear cells. Indeed, we observed an enrichment of X4 viruses after replication in thymocytes initially infected with a mixture of X4 (NL4-3) and R5 (NLAD8) HIV strains and after the emergence of X4 variants from an R5 primary isolate during culture in mature thymocytes.

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“…A major complication of lentivirus infection is the accelerated thymic involution observed in HIV-1-infected humans and FIV-infected cats (24) with the associated loss of thymic function and subsequent CD4 ϩ T-lymphocyte depletion (5,24). Thymic changes are most pronounced in pediatric subjects where HIV-1 (18,21) and FIV (9,24) infections cause structural damage to the thymus, manifested by depletion of CD4 ϩ…”

mentioning

confidence: 99%

Lentivirus-Specific Cytotoxic T-Lymphocyte Responses Are Rapidly Lost in Thymectomized Cats Infected with Feline Immunodeficiency Virus

Hayes¹,

Köksoy²,

Phipps³

et al. 2005

J Virol

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To what extent the thymus is needed to preserve the virus-specific cytotoxic T-lymphocyte (CTL) response of lentivirus-infected adults is unclear. Presented here is the first definitive study using thymectomized (ThX) animals to directly evaluate the contribution of thymic function to lentivirus-specific CTL response and the control of lentivirus infections. ThX and mock-ThX cats were inoculated with feline immunodeficiency virus (FIV) and monitored for their FIV-specific CTL responses. Early in infection, both FIV-ThX and FIV-mockThX cats produced similar CTL responses, but surprisingly, after 20 weeks, the FIV-ThX cats showed a statistically significant loss of FIV-specific CTL activity, while FIV-infected cats with intact thymuses continued to maintain FIV-specific CTL. The loss of CTL did not affect plasma virus load, which remained elevated for both groups. These results emphasize the importance of thymic integrity in maintaining immunity to lentiviruses, but also bring into question the notion that virus load is regulated predominantly by the virus-specific CTL response.

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Thymic size on chest radiograph and rapid disease progression in human immunodeficiency virus 1-infected children

Abstract: Early thymic involution is associated with rapidly progressive disease in HIV-infected children.

Cited by 21 publications

References 30 publications

Thymus Involution and Cerebral White Matter Damage in Extremely Low Gestational Age Neonates

Thymus Involution and Cerebral White Matter Damage in Extremely Low Gestational Age Neonates

Positive Regulation of CXCR4 Expression and Signaling by Interleukin-7 in CD4⁺Mature Thymocytes Correlates with Their Capacity To Favor Human Immunodeficiency X4 Virus Replication

Lentivirus-Specific Cytotoxic T-Lymphocyte Responses Are Rapidly Lost in Thymectomized Cats Infected with Feline Immunodeficiency Virus

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Thymic size on chest radiograph and rapid disease progression in human immunodeficiency virus 1-infected children

Abstract: Early thymic involution is associated with rapidly progressive disease in HIV-infected children.

Cited by 21 publications

References 30 publications

Thymus Involution and Cerebral White Matter Damage in Extremely Low Gestational Age Neonates

Thymus Involution and Cerebral White Matter Damage in Extremely Low Gestational Age Neonates

Positive Regulation of CXCR4 Expression and Signaling by Interleukin-7 in CD4+Mature Thymocytes Correlates with Their Capacity To Favor Human Immunodeficiency X4 Virus Replication

Lentivirus-Specific Cytotoxic T-Lymphocyte Responses Are Rapidly Lost in Thymectomized Cats Infected with Feline Immunodeficiency Virus

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Positive Regulation of CXCR4 Expression and Signaling by Interleukin-7 in CD4⁺Mature Thymocytes Correlates with Their Capacity To Favor Human Immunodeficiency X4 Virus Replication