CD80/CD86 AND CD28/CD152 IN CELLULAR IMMUNOREACTIONS

A293 Aims: Submit a hypothesis of new model to illustrate the co-stimulators performance, which including B-1 (CD80) and B7-2 (CD86) and their receptors CD28 and CD152. Backgrounds: Recent literatures and our experimental outcomes have illustrated the characteristic of the four molecules: 1.Considering both affinity and combing efficiency, the final effects among four co-stimulators are: CD80-CD152 > CD86-CD152, CD86-CD28 > CD80-CD28. 2. MHC class I molecules and CD80 are abundantly expressed on immature DCs instead of MHC class II molecules and CD86, while CD28 is the major co-stimulator on immature T cells. 3. CD28 or CD152 doesn’t simply make a positive or negative effect in immunoreactions. Evidences indicate that stimulation of CD28 will induce T cells into a proliferating state while CD152 may play an important role in promoting their maturation as well as inhibiting their proliferation. Therefore, the functions of CD28 and CD152 are cooperated indeed. Assumptions: The immunoreactions in vivo take place incessantly on an imperceptible level. In resting state of immature APCs, such few antigens are endocyted that they are not able to induce the maturation of APCs. Therefore immature APCs and naïve T cells are responsible for the baseline of immunoreactions, in which the signal 1 is MHC I-antigen-TCR, and signal 2 is CD80-CD28. When the amount of antigens reaches to limen, the endocytosis of them will promote APCs into mature state, which is characterized by the substitutive expression of MHC II as well as marked up-regulation of CD86. Therefore the two signals are gradually substituted into MHC II-antigen-TCR and CD86-CD28. The immunoreactions go up and the proliferation efficiency of T cells goes to the fastigium. As certain cytokines work and CD86-CD28 feed back, transportation of CD152 are promoted from intracellular vesicles to the membrane of T cells, which makes the ratio of CD152/CD28 goes up and subsequently lead to the ligation of CD86-CD152. As is mentioned above, the activation of CD152 may promote the cellular immunity and make the curve of immunoreactions continue to ascend. As the combination efficiency of CD80-CD152 is 3-folder greater than CD80-CD28, the former will finally take the place of the latter. Negative cytokines and ligation of CD152 will then induce the programmed death of T cells, which finally leads to the descending of inflammation to the baseline (figure 1).FigureConclusions: The orderly expression and competitive ligations of co-stimulators makes them cooperate with each other, which ensures cell maturation to clear out pathogens quickly and avoids over-proliferation to cause inflammation. Quantitative change leads to qualitative change, which illustrates the procedure of immunoreactions macroscopically as in figure 2. It shows that the fastigium of APCs and T cells proliferating will appear at the ligation period of CD80-CD28, while that of immunoreactions at CD86-CD152.Figure