Morphological Changes of Thymus in Retrovirus-Induced Murine Acquired Immunodeficiency Syndrome (MAIDS)

Leval, Laurence de; Deprez, Manuel; Colombi, S.; Humblet, Chantal; Defresne, Marie-Paule; Boniver, Jacques; Moutschen, Michel

doi:10.1016/s0344-0338(11)80869-1

Cited by 6 publications

(5 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In some mice, but not all, thymi from 70 dpi reveal a lack of clear distinction between cortex and medulla and an overall increased expression of K5 and K8. This type of disorganized thymic structure has been previously observed during HIV (60)(61)(62), MuLV (63), Leishmania infantum (64) and P. berghei (65) infections.…”

Section: Discussionsupporting

confidence: 69%

IFNγ and iNOS-Mediated Alterations in the Bone Marrow and Thymus and Its Impact on Mycobacterium avium-Induced Thymic Atrophy

et al. 2021

View full text Add to dashboard Cite

Disseminated infection with the high virulence strain of Mycobacterium avium 25291 leads to progressive thymic atrophy. We previously showed that M. avium-induced thymic atrophy results from increased glucocorticoid levels that synergize with nitric oxide (NO) produced by interferon gamma (IFNγ) activated macrophages. Where and how these mediators act is not understood. We hypothesized that IFNγ and NO promote thymic atrophy through their effects on bone marrow (BM) T cell precursors and T cell differentiation in the thymus. We show that M. avium infection cause a reduction in the percentage and number of common lymphoid progenitors (CLP). Additionally, BM precursors from infected mice show an overall impaired ability to reconstitute thymi of RAGKO mice, in part due to IFNγ. Thymi from infected mice present an IFNγ and NO-driven inflammation. When transplanted under the kidney capsule of uninfected mice, thymi from infected mice are unable to sustain T cell differentiation. Finally, we observed increased thymocyte death via apoptosis after infection, independent of both IFNγ and iNOS; and a decrease on active caspase-3 positive thymocytes, which is not observed in the absence of iNOS expression. Together our data suggests that M. avium-induced thymic atrophy results from a combination of defects mediated by IFNγ and NO, including alterations in the BM T cell precursors, the thymic structure and the thymocyte differentiation.

show abstract

Section: Discussionsupporting

confidence: 69%

IFNγ and iNOS-Mediated Alterations in the Bone Marrow and Thymus and Its Impact on Mycobacterium avium-Induced Thymic Atrophy

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In addition, studies in mice infected with LP-BM5 retrovirus have shown similar results characterized by a marked reduction in the percentage of CD4 þ CD8 þ thymocytes (Lopez et al 1992a(Lopez et al ,b, 1993Colombi et al 1994;de Leval et al 1995 Figure 5A, 6B, C, E and F).…”

Section: Changes In Surface Markers Expression On Thymocytes Of Retromentioning

confidence: 54%

“…In previous studies, we have shown a decrease in the number of thymocytes after LP-BM5 infection (Lopez et al 1992a,b) as well as a decrease in the percentage of double positive CD4CD8 thymocytes (Lopez et al 1992a) and the disappearance of the cortical areas of the thymus 11 weeks after infection (Lopez et al 1993 (Lopez et al 1992a;Colombi et al 1994;de Leval et al 1995). The triple staining analysis done in this study allowed us to show that not all single positive cells found in the thymus are mature and therefore express CD3, on the contrary, immature precursors also accumulated.…”

Section: Discussionmentioning

confidence: 86%

“…Even though LP-BM5 favors the proliferation of CD4 þ cells, instead of inducing their depletion as HIV does, it renders them anergic and therefore, useless to protect the host (Muralidhar et al 1992). Furthermore, it has been demonstrated that LP-BM5 also reaches the thymus and depletes it of double positive CD4CD8 cells (Lopez et al 1992a(Lopez et al ,b, 1993de Leval et al 1995;Colombi et al 1994) as has been shown for HIV in the elegant experiments using SCID mice reconstituted with neonatal thymus that were later on infected with the virus (Stanley et al 1993;Bonyhadi and Kaneshima 1997).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Alterations in Mesenteric Lymph Node T Cell Phenotype and Cytokine Secretion are Associated with Changes in Thymocyte Phenotype after LP‐BM5 Retrovirus Infection

López

Watson

2005

Journal of Immunology Research

View full text Add to dashboard Cite

In this study, mouse MLN cells and thymocytes from advanced stages of LP-BM5 retrovirus infection were studied. A decrease in the percentage of IL-7 þ cells and an increase in the percentage of IL-16 þ cells in the MLN indicated that secretion of these cytokines was also altered after LP-BM5 infection. The percentage of MLN T cells expressing IL-7 receptors was significantly reduced, while the percentage of MLN T cells expressing TNFR-p75 and of B cells expressing TNFR-p55 increased. Simultaneous analysis of surface markers and cytokine secretion was done in an attempt to understand whether the deregulation of IFN-g secretion could be ascribed to a defined cell phenotype, concluding that all T cell subsets studied increased IFN-g secretion after retrovirus infection. Finally, thymocyte phenotype was further analyzed trying to correlate changes in thymocyte phenotype with MLN cell phenotype. The results indicated that the increase in single positive either CD4 þ CD8 2 or CD4 2 CD8 þ cells was due to accumulation of both immature (CD3 2 ) and mature (CD3 þ ) single positive thymocytes. Moreover, single positive mature thymocytes presented a phenotype similar to the phenotype previously seen on MLN T cells. In summary, we can conclude that LP-BM5 uses the immune system to reach the thymus where it interferes with the generation of functionally mature T cells, favoring the development of T cells with an abnormal phenotype. These new T cells are activated to secrete several cytokines that in turn will favor retrovirus replication and inhibit any attempt of the immune system to control infection.

show abstract

“…Immunodeficiency virus is a retrovirus that affects a variety of animals in addition to humans ( 47 ). In human acquired immunodeficiency syndrome (AIDS), severe thymocyte depletion restricts T cell production in the thymus, which is the main pathogenesis of human immunodeficiency virus (HIV).…”

Section: Virusesmentioning

confidence: 99%

Infection-Associated Thymic Atrophy

Ming-li

Qian

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

The thymus is a vital organ of the immune system that plays an essential role in thymocyte development and maturation. Thymic atrophy occurs with age (physiological thymic atrophy) or as a result of viral, bacterial, parasitic or fungal infection (pathological thymic atrophy). Thymic atrophy directly results in loss of thymocytes and/or destruction of the thymic architecture, and indirectly leads to a decrease in naïve T cells and limited T cell receptor diversity. Thus, it is important to recognize the causes and mechanisms that induce thymic atrophy. In this review, we highlight current progress in infection-associated pathogenic thymic atrophy and discuss its possible mechanisms. In addition, we discuss whether extracellular vesicles/exosomes could be potential carriers of pathogenic substances to the thymus, and potential drugs for the treatment of thymic atrophy. Having acknowledged that most current research is limited to serological aspects, we look forward to the possibility of extending future work regarding the impact of neural modulation on thymic atrophy.

show abstract

Morphological Changes of Thymus in Retrovirus-Induced Murine Acquired Immunodeficiency Syndrome (MAIDS)

Cited by 6 publications

References 12 publications

IFNγ and iNOS-Mediated Alterations in the Bone Marrow and Thymus and Its Impact on Mycobacterium avium-Induced Thymic Atrophy

IFNγ and iNOS-Mediated Alterations in the Bone Marrow and Thymus and Its Impact on Mycobacterium avium-Induced Thymic Atrophy

Alterations in Mesenteric Lymph Node T Cell Phenotype and Cytokine Secretion are Associated with Changes in Thymocyte Phenotype after LP‐BM5 Retrovirus Infection

Infection-Associated Thymic Atrophy

Contact Info

Product

Resources

About