The Histopathological Changes in the Thymus Gland in the Acquired Immune Deficiency Syndrome

Davis, Arthur E.

doi:10.1111/j.1749-6632.1984.tb37173.x

Cited by 25 publications

(13 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Viral infection is clearly associated with thymic pathology in HIV-1-infected humans (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36), and SCID-hu mice (37)(38)(39)(40), simian immunodeficiency virus-infected nonhuman primates (41)(42)(43), and feline immunodeficiency virus-infected cats (44,45 …”

Section: Introductionmentioning

confidence: 99%

High prevalence of thymic tissue in adults with human immunodeficiency virus-1 infection.

McCune¹,

Loftus²,

Schmidt³

et al. 1998

J. Clin. Invest.

244

149

View full text Add to dashboard Cite

The thymus in adults infected with the HIV-1 is generally thought to be inactive, both because of age-related involution and viral destruction. We have revisited the question of thymic function in adults, using chest-computed tomography (CT) to measure thymic tissue in HIV-1-seropositive ( n ϭ 99) or HIV-1-seronegative ( n ϭ 32) subjects, and correlating these results with the level of circulating CD4 ϩ and CD8 ϩ T cells that are phenotypically described as naive thymic emigrants. Abundant thymic tissue was detectable in many (47/99) HIV-1-seropositive adults, aged 20-59. Independent of age, radiographic demonstration of thymic tissue was significantly associated with both a higher CD4 ϩ T cell count ( P ϭ 0.02) and a higher percentage and absolute number of circulating naive (CD45RA ϩ CD62L ϩ ) CD4 ϩ T cells ( P Ͻ 0.04). The prevalence of an abundant thymus was especially high in younger HIV-1-seropositive adults ( Յ 39 yr) with CD4 counts in the range 300-500 cells/ l and in older subjects ( Ͼ 40 yr) regardless of CD4 count ( P ϭ 0.03). These studies suggest that the thymus is functional in some but not all adults with HIV-1 disease. ( J. Clin. Invest. 1998.

show abstract

Section: Introductionmentioning

confidence: 99%

High prevalence of thymic tissue in adults with human immunodeficiency virus-1 infection.

McCune¹,

Loftus²,

Schmidt³

et al. 1998

J. Clin. Invest.

244

149

View full text Add to dashboard Cite

show abstract

“…In human immunodeficiency virus type 1 (HIV-1) infection, the thymus carries a heavy viral burden and is decimated by the cytopathic effects of the virus on thymocytes as well as supporting stromal elements (4,6). The effects of thymic infection are especially devastating in HIV-1-infected children, where destruction of the thymus occurs while thymic function is still needed for the generation of antigenically diverse T lymphocytes (23,24).…”

mentioning

confidence: 99%

“…The effects of thymic infection are especially devastating in HIV-1-infected children, where destruction of the thymus occurs while thymic function is still needed for the generation of antigenically diverse T lymphocytes (23,24). HIV-related accelerated thymic involution is a common histological finding in pediatric AIDS and is marked by severe depletion of both lymphoid and epithelial cells (5,6). Thymitis and dysinvolution also are common features which may precede the accelerated involution associated with pediatric AIDS (5,14,25).…”

mentioning

confidence: 99%

Antiviral Therapy Reduces Viral Burden but Does Not Prevent Thymic Involution in Young Cats Infected with Feline Immunodeficiency Virus

Hayes¹,

Phipps²,

Francke³

et al. 2000

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The thymus is a major target organ in human immunodeficiency virus type 1 (HIV-1)-infected children and feline immunodeficiency virus (FIV)-infected young cats (G.A. The purpose of this study was to evaluate the effect of drug-induced reduction of viral burden in the thymus on virusmediated thymic involution and peripheral blood CD4 decline using FIV-infected cats as a model for pediatric HIV-1 infection. Eight-week-old cats were randomly assigned to uninfected, saline-treated; uninfected, ZDVtreated; FIV-infected, saline-treated; and FIV-infected, ZDV-treated groups. Parameters measured included blood lymphocyte numbers, viral load in blood and thymic tissue, and thymic histopathology. While the viral burden was significantly reduced by ZDV monotherapy in peripheral blood lymphocytes, plasma, and thymus, thymic lesions were similar for the treated and untreated FIV-infected cats. Further, markedly lowering the viral burden did not increase blood CD4 lymphocyte numbers or prevent their decline. The data suggest that an inflammatory process continued in spite of reduced virus replication. These observations imply that reducing virus load and limiting thymic inflammation are separate factors that must be addressed when considering therapeutic strategies aimed at preserving thymic function.

show abstract

“…HIV-1 infection of the thymus has been demonstrated in autopsy specimens from HIV-1-infected fetuses and patients (7)(8)(9)(10)(11)(12) as well as in experimental infection of both ex vivo thymic tissue and the SCID-hu Thy/Liv mouse (13,14). In children with perinatal HIV-1 disease, thymic infection is associated with low peripheral T cell counts of both the CD4 and CD8 lineages and with rapid disease progression.…”

mentioning

confidence: 99%

Generation of CD3+CD8low Thymocytes in the HIV Type 1-Infected Thymus

Keir

Rosenberg

Sandberg

et al. 2002

The Journal of Immunology

View full text Add to dashboard Cite

Infection with the HIV type 1 (HIV-1) can result both in depletion of CD4+ T cells and in the generation of dysfunctional CD8+ T cells. In HIV-1-infected children, repopulation of the peripheral T cell pool is mediated by the thymus, which is itself susceptible to HIV-1 infection. Previous work has shown that MHC class I (MHC I) molecules are strongly up-regulated as result of IFN-α secretion in the HIV-1-infected thymus. We demonstrate in this study that increased MHC I up-regulation on thymic epithelial cells and double-positive CD3−/intCD4+CD8+ thymocytes correlates with the generation of mature single-positive CD4−CD8+ thymocytes that have low expression of CD8. Treatment of HIV-1-infected thymus with highly active antiretroviral therapy normalizes MHC I expression and surface CD8 expression on such CD4−CD8+ thymocytes. In pediatric patients with possible HIV-1 infection of the thymus, a low CD3 percentage in the peripheral circulation is also associated with a CD8low phenotype on circulating CD3+CD8+ T cells. Furthermore, CD8low peripheral T cells from these HIV-1+ pediatric patients are less responsive to stimulation by Ags from CMV. These data indicate that IFN-α-mediated MHC I up-regulation on thymic epithelial cells may lead to high avidity interactions with developing double-positive thymocytes and drive the selection of dysfunctional CD3+CD8low T cells. We suggest that this HIV-1-initiated selection process may contribute to the generation of dysfunctional CD8+ T cells in HIV-1-infected patients.

show abstract

The Histopathological Changes in the Thymus Gland in the Acquired Immune Deficiency Syndrome

Cited by 25 publications

References 14 publications

High prevalence of thymic tissue in adults with human immunodeficiency virus-1 infection.

High prevalence of thymic tissue in adults with human immunodeficiency virus-1 infection.

Antiviral Therapy Reduces Viral Burden but Does Not Prevent Thymic Involution in Young Cats Infected with Feline Immunodeficiency Virus

Generation of CD3+CD8low Thymocytes in the HIV Type 1-Infected Thymus

Contact Info

Product

Resources

About