T Lymphocyte Subpopulation & Modulatory Expression Of Correlative Molecules In The Process Of Physiological Senescence

Senescence can be defined as all-directions, multisystems, gradual advance and gene controlled strictly physiological natural process accompany with aging. The catholicity, inner causation, proceeding and harmfulness considered as standard of Senescence have been well known. Kinds of parties and numerous hypothesizes occurred in long-term quest toward senescence mechanism. However, hypothesis that weak immune function would accelerate senescence process were concerned more and more. Many researches shown that person of advanced age was prone to be infected comparing with younger, particularly their immune response reduced obviously when got in touch with new antigens which they had never experienced. So paroxysm occurrence and development of disease not only made living quality descent, even might threaten their life, and thus the weak immune function turn into one of the important reason of physiological senescence.Although the theory that weak immunity function plays an important role in paroxysm and development of disease has been widely accepted, the mechanism how the immune system acted in the process of senescence has not been understood clearly. Recent researches showed that, compared with young individuals, the subpopulations of T cell in the elder change obviously, for example, CD3+ T cells and CD4+ T cells decrease, contrarily CD8+ Tcells increase, naive T cells drop but memory T cells climb, CD28 expressed in T cells fall, concentration of IL-2 in plasma goes down. But for IL-4 and IL-6, controversy existed. Most of people consider that its concentration increase, others held the different standpoint.In our research, we further studied the absolute and relative number of T cell and its subpopulation, the expression of CD28 on T cell subpopulation, sCD28, IL-2, IL-4 concentrations in plasma of each groups, and made preliminary discussion the senescence mechanism.1. T cell subpopulation and expression of costimulatory molecules in peripheral blood of senescence.Absolute and relative value of CD3+ T cell, CD4+ T cell, CD8+ T cell, CD45RA+ T cell, CD45RO+ T cell and the costimulatory molecule CD28+ T cell in 513 individual above 20 years old were analyzed with blood cell autoanalyzer and Flow CytoMetry. Results showed that, along with the age, absolute and relative value of CD3+ T cell and CD4+ T cell decreased gradually, however, CD8+ T cell increased gently, the rate of CD4+T cell/CD8+T cell also decreased, naive T cell reduced but memory cell augmented. CD28+ T cell reduced continuously, and then both expression of CD4+CD28+ T cell and CD8+CD28+ T cell decreased accordingly, CD25+ T cell added in succession.Results also made clear that, either absolute value or relative value, no remarkable differences were observed before 60 years old. But when age reached 60 years old, especially above 80 years old, it was different, indicating that 60 years old would be very important turning point of immune function. In addition, the correlation coefficient of each value with age was all right, indicating that all of those value were significant in the process of senescence.2. Concentration measurement of cytokine IL-2, IL-4, IL-6 and soluble CD28 in plasma.Concentration of the cytokine IL-2, IL-4, IL-6 and sCD28 in 300 plasma of healthy individuals above 20 years old were analyzed by Flow CytoMetry or ELISA method. Results showed that, along with aging, concentration of cytokine IL-2 decreased gradually, on the contrary, concentration of cytokine IL-4, IL-6 and sCD28 raised continuously. Especially, the concentration of cytokine IL-4 climbed rapidly when age reached 70 years old. Result also revealed that no difference existed before 60 years old, but changed in age above 60 years old, especially above 80 years old. In addition, the four indexes all correlated with aging.Correlation existed between sCD28 and CD4+CD28+T, CD8+CD28+T cell, therefore it was very the reason that sCD28 were from CD28 in CD4+T and CD8+T cell.Our experiment also revealed that sCD28 was correlated with IL-6 concentration. The reason was that sCD28 in plasma could be combined with B7-1 molecule in dendritic cell, resulting in production of IL-6 from DC in order to enhance immune function. So it was worth further studying whether the accumulation of sCD28 concomitance with aging and abnormal activation of DC was related with autoimmune diseases.Conclusions:Remarkable immune variety occurred in the elderly when compared to young people including T cells and its subpopulations, naive and memory T cell, costimulatory CD28, CD25+ T cell, cytokine IL-2, DL-4, IL-6 and sCD28. Any more, this variety was incessantly along with whole life, especially 60 and 80 years old were two important point of obviously changing, indicating that one should take notably notice on healthy whenabove 60 years old.Soluble CD28 was possibly come from CD28 in CD4+T and CD8+T cell after long-term antigen stimulation. It was the action between sCD28 in plasma and B7-1 in Dc that result in production of IL-6.In conclusion, our research further demonstrated the theory of immunosenescence. Perhaps these conclusions may provide important theories for intervention of senescence or further life-prolong.