| Thymus is the site for T cell differentiation, maturation, and selection. These three interrelated processes lead to the production of mature function T cells. Following selection through the pre-T-cell receptor(pre-TCR), early CD4-CD8- cells(2-3% of adult thymocytes, many of which are dividing ) acquire CD4 and CD8 on the cell surface, and become 'double-positive'(DP) thymocytes. The early, large DP cells (10-15% of all thymocytes) divide several times before they stop proliferating and become small DP cells (70% of all thymocytes). DP thymocytes make up the bulk of cells in the thymic cortex. Most DP cells die, either by defult(no positive selection) or by negative selection.A small proportion of DP cells survive after thymic selection and become CD4+CD8- or CD4-CD8+ 'single-positive' (SP) thymocytes, the majority of which are located in the thymic medulla and express higher levels of TCR.In contrast to the cortex, the thymic medulla is generally considered to be a relatively inactive compartment, where little cell divisions occurs, cell death is minimal and cells predominantly await export to the periphery. However, this point of view has been challenged recently. The average medullery residence time of SP thymocytes is almost 14 days. During this period, final maturation process may take place. Functional maturation process of medullary-type CD4+CD8 and CD4"CD8+ thymocytes remains largely unclear. To this end, it is necessary to define the subgroups among these cells. Anti-TCR monoclonal antibodies are potent apoptosis-inducing agents at pharmacological and physiological doses on Tlymphocytes. The activation of peripheral T lymphocytes could be stimulated by anti-TCRαβAb , ConA and PMA+Ionomycin, the latter activated both T and B lymphocytes. The effects of different stimuli on the division of T lymphocytes were different, as shown in the order of: PMA+Ionomycin> ConA > anti-TCRapmAb. The same rule was also applicable to thymocyte proliferation. However, the frequency and dividing times of thymocytes were far less than those of peripheral T lymphocytes due to their different degree of cell maturity.Analysis the susceptibility of different subsets of immature mice thymocytes to undergo apoptosis. In Vitro apoptosis was induced in unfractionated mice thymocytes by anti-TCR mAbs.In Vivo apoptosis was induced in BALB/c mice by anti-TCR mAbs ,and thymocytes were examined for it by FACS. Results showed that CD4+CD8+DP thymocytes and CD4-CD8+CD3- thymocytes were equally sensitive to apoptosis after treatment with the anti-TCR mAbs. In sharp contrast, the early migrants or precursor-containing thymocytes which are CD4-CD8-CD3- TN have a lower spontaneous apoptosis rate and were relativel resistant to the anti-TCR mAbs. The findings showed a breakpoint in thymocyte sensitivity to apoptosis which occurs after the onset of CD8 expression, suggesting that susceptibility of thymocytes to apoptosis is developmentally regulated.With regard to distribution of immune cells, no significant sex-related changes were seen in thymocyte expression of CD3, CD8, CD4 or splenocyte expression of CD3 , CD8, CD4.For splenocytes, significantly more cells were positive for CD3 in 6-9 week old compared with 3-4 weekold mice. Thymocyte proliferation was not related to age or sex of the mice. For splenocytes of the 3 weeks old mice, the response to a cell of PMA and ionomycin induced a significantly greater then that by cells from females. For mice 7-8 weeks of age, splenocytes from female mice responded significantly less to stimulation by antibody to TCR. Conclusion Sexual dimorphism in the immune system may be demonstrated prior to puberty.Investigate a link between anti-TCRmAb-induced apoptosis in mice thymocytes and sex. Apoptosis of thymocytes was studied in male and female mice by in intraperitionealy injection with anti-TCRmAb and cell culture with anti-TCR raAb added, and a possible link between apoptosis sensitivity and cell cycle was also analyzed. The mice showed a slight increase in the total number of m... |
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