Abstract
Thymocytes can be divided into four major subpopulations: CD4 +CD8 + (double-positive), CD4 −CD8 − (double-negative), CD4 +CD8 − (CD4 +) and CD4 −CD8 + (CD8 +) cells. Recent studies have shown that T-cell development in the thymus progresses as: CD4 −CD8 − → CD4 +CD8 + → CD4 + or CD8 + cells. In the present study we investigated these and other subpopulations of thymocytes in autoimmune MRL-+/+, MRL- lpr lpr , C57BL 6 - lpr lpr , BXSB and NZB mice before (1-month old) and after (4–6-months old) the onset of lymphadenopathy and autoimmune disease. All the autoimmune strains at one month of age and other H-2, sex and age-matched controls (C3H, DBA 2 , and C57BL 6 ) demonstrated normal proportions of thymocyte subsets with ∼75% double-positive cells, 5–7% double-negative cells, 11–15% CD4 + cells and 3–5% CD8 + cells. By 4–6 months of age, MRL-+/+ mice demonstrated a moderate increase in double-negative cells (∼13%) and a decrease in double-positive cells (∼46%). Interestingly, in the presence of the lpr gene, as seen in MRL- lpr lpr mice, the double-negative cells increased to ∼47% and the double-positive cells decreased to ∼16%. In contrast, 4–6-month-old C57BL 6 - lpr lpr mice failed to demonstrate any alterations in the thymocyte subsets thereby suggesting that background genes, in addition to the lpr gene, played a role in the thymocyte differentiation. BXSB male mice with severe lymphadenopathy behaved very similarly to MRL- lpr lpr mice, inasmuch as their thymus contained ∼48% double-negative cells and only ∼8% double-positive cells. In contrast to MRL- lpr lpr and BXSB strains, NZB mice at 6 or 10 months of age had normal composition of thymocyte subsets. In MRL and BXSB animals, although there was a significant increase in CD4 + cells (∼23–33%), due to a consequent increase in CD8 + cells (∼11%), the ratio of CD4 +:CD8 + cells remained 2–3:1, similar to that seen in normal mice. Furthermore, using the J11d marker expressed by the majority of the double-negative and all double-positive thymocytes but not by mature functional T cells, we confirmed the above findings and demonstrated further that MRL- lpr lpr mice at 4–6 months of age had an increased percentage of J11d − double-negative cells and a decrease in J11d + double-negative cells. The present study demonstrates for the first time the existence of a common defect in T-cell differentiation in the thymus of autoimmune strains of mice which is dependent on the genetic background and other accelerating factors responsible for inducing autoimmune disease.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.