1990 Fiscal Year Final Research Report Summary
The Role of Accessory Cells in the Induction of Receptor-Mediated Human T Cell Growth.
Grant-in-Aid for General Scientific Research (B)
|Allocation Type||Single-year Grants|
|Research Institution||Kumamoto University|
KAKIMOTO Kiichi Kumamoto University Medical School, Institute for Medical Immunology, Department of Biochemistry, Associate Professor, 医学部, 助教授 (20112352)
OHMURA Takafumi Kumamoto University Medical School, Institute for Medical Immunology, Department, 医学部, 助手 (30185384)
ONOUE Kaoru Kumamoto University Medical School, Institute for Immunology, Department of Bioc, 医学部, 教授 (60037497)
|Project Period (FY)
1989 – 1990
|Keywords||Accessory cell function / T-macrophage interaction / T cell proliferation / Interferon-gamma / Sur face-interaction molecules / LFA-1 / ICAM-1 / LFAー1|
The present study was performed to made clear at molecular level the functions of accessory cells (AC) mediated by soluble factors released from AC and by cell-surface interaction between AC and T cells which are required for the induction of receptor-mediated human T cell proliferation.
To dissect the AC functions into factor-mediated and cell contact-mediated functions, the AC-depleted peripheral blood (PB)-T cells were stimulated with anti-CD3-antibody coated on latex beads in a culture with or without macrophagederived soluble factors and paraformaldehyde (PFA)-fixed macrophages (f-Mo) and the T cell proliferation was examined. Major findings obtained in this study are summarized as follows.
1) Both the factor-mediated and cell-contact-mediated accessory functions are required for the induction of the T cell proliferation.
2) The soluble factors required were found to be IL-1 and IL-6. Both of these factors are indispensable because addition of either one of recombinant IL-1beta or IL
-6 alone did not induce T cell proliferation, and the activity of Monoculture supernatant were diminished by adding either one of the neutralizing antibodies to IL-1beta or IL-6.
3) A significant discovery in this study is that, before PFA-fixation, the macrophages had to be cultured with Con A-stimulated PB-mononuclear cells or interferon-gamma (IFN-gamma) to induce T cell proliferation. These results indicate that the expression of a certain cell-surface molecule (s) is induced by T cell-derived lymphokine (IFN-gamma) and this molecule is essential for the AC-T cell interaction.
4) For AC-T cell interaction, inhibition studies with monoclinal antibodies (mAb) showed that interaction through LFA-1 and ICAM-1 is essential. In addition, a 200 Kd pan-leukocyte antigen was also shown to contribute significantly. This molecule is recognized by a mAd KW-23, raised in this study and appears to be a novel cell-interaction molecule.
Thus our study demonstrated the dynamic bi-directional interaction between Mo and T cells. We proposed that, during the interaction, at least one of the necessary cell-interaction molecule is induced by IFN-gamma released from T cells. The Mo-T cell-interaction and soluble factors (IL-1 and IL-6) released from Mo induce IL-2 production and T cell proliferation. Less
Research Products (7results)