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Comparative analysis of thymic subpopulations during different modes of atrophy identifies the reactive oxygen species scavenger, N-acetyl cysteine, to increase the survival of thymocytes during infection-induced and lipopolysaccharide-induced thymic atrophy

Majumdar, Shamik and Adiga, Vasista and Raghavan, Abinaya and Rananaware, Supriya Rajendra and Nandi, Dipankar (2019) Comparative analysis of thymic subpopulations during different modes of atrophy identifies the reactive oxygen species scavenger, N-acetyl cysteine, to increase the survival of thymocytes during infection-induced and lipopolysaccharide-induced thymic atrophy. In: IMMUNOLOGY, 157 (1). pp. 21-36.

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Official URL: https://doi.org/10.1111/imm.13043

Abstract

The development of immunocompetent T cells entails a complex pathway of differentiation in the thymus. Thymic atrophy occurs with ageing and during conditions such as malnutrition, infections and cancer chemotherapy. The comparative changes in thymic subsets under different modes of thymic atrophy and the mechanisms involved are not well characterized. These aspects were investigated, using mice infected with Salmonella Typhimurium, injection with lipopolysaccharide (LPS), an inflammatory but non-infectious stimulus, etoposide (Eto), a drug used to treat some cancers, and dexamethasone (Dex), a steroid used in some inflammatory diseases. The effects on the major subpopulations of thymocytes based on multicolour flow cytometry studies were, first, the CD4(-)CD8(-) double-negative (DN) cells, mainly DN2-4, were reduced with infection, LPS and Eto treatment, but not with Dex. Second, the CD8(+)CD3(lo) immature single-positive cells (ISPs) were highly sensitive to infection, LPS and Eto, but not Dex. Third, treatment with LPS, Eto and Dex reduced all three subpopulations of CD4(+)CD8(+) double-positive (DP) thymocytes, i.e. DP1, DP2 and DP3, but the DP3 subset was relatively more resistant during infection. Fourth, both CD4(+) and CD8(+) single-positive (SP) thymocytes were lowered by Eto and Dex, but not during infection. Notably, LPS lowered CD4(+) SP subsets, whereas the CD8(+) SP subsets were relatively more resistant. Interestingly, the reactive oxygen species quencher, N-acetyl cysteine, greatly improved the survival of thymocytes, especially DNs, ISPs and DPs, during infection and LPS treatment. The implications of these observations for the development of potential thymopoietic drugs are discussed.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to WILEY
Keywords: infection; lipopolysaccharide; reactive oxygen species; thymic atrophy; thymocyte subpopulations
Department/Centre: Division of Biological Sciences > Biochemistry
Division of Biological Sciences > Centre for Infectious Disease Research
Depositing User: R.S. Ranganayaki
Date Deposited: 27 May 2019 06:13
Last Modified: 29 May 2019 09:16
URI: http://eprints.iisc.ac.in/id/eprint/62650

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