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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
Author(s) -
Majumdar Shamik,
Adiga Vasista,
Raghavan Abinaya,
Rananaware Supriya Rajendra,
Nandi Dipankar
Publication year - 2019
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.13043
Subject(s) - cd8 , biology , thymocyte , lipopolysaccharide , atrophy , immunology , flow cytometry , dexamethasone , double negative , immune system , endocrinology , genetics
Summary 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 CD 4 − CD 8 − double‐negative ( DN ) cells, mainly DN 2–4, were reduced with infection, LPS and Eto treatment, but not with Dex. Second, the CD 8 + CD 3 lo immature single‐positive cells ( ISP s) were highly sensitive to infection, LPS and Eto, but not Dex. Third, treatment with LPS , Eto and Dex reduced all three subpopulations of CD 4 + CD 8 + double‐positive ( DP ) thymocytes, i.e. DP 1, DP 2 and DP 3, but the DP 3 subset was relatively more resistant during infection. Fourth, both CD 4 + and CD 8 + single‐positive ( SP ) thymocytes were lowered by Eto and Dex, but not during infection. Notably, LPS lowered CD 4 + SP subsets, whereas the CD 8 + SP subsets were relatively more resistant. Interestingly, the reactive oxygen species quencher, N ‐acetyl cysteine, greatly improved the survival of thymocytes, especially DN s, ISP s and DP s, during infection and LPS treatment. The implications of these observations for the development of potential thymopoietic drugs are discussed.