CO-ENGAGEMENT OF CD3 WITH LFA-1 OR ICAM-1 ADHESION MOLECULES ENHANCES THE FREQUENCY OF ACTIVATION OF SINGLE MURINE CD4+ AND CD8+ T-CELLS AND INDUCES SYNTHESIS OF IL-3 AND IFN-GAMMA BUT NOT IL-4 OR IL-6

Maraskovsky, E; TROUTT, AB; Kelso, A

Author(s): Maraskovsky, E; TROUTT, AB; Kelso, A;
Details: Publication Year 1992-04,Volume 4,Issue #4,Page 475-485
Journal Title: INTERNATIONAL IMMUNOLOGY
Publication Type: Journal Article
Abstract: Interaction between the cell adhesion molecules lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) augments T cell activation by increasing the avidity of T cell/antigen-presenting cell (APC) binding. To examine whether LFA-1 and ICAM-1 can also contribute to T cell activation in the absence of APCs, single murine CD4+ and CD8+ T cells were cultured with IL-2 and immobilized antibodies to CD3, CD4 or CD8, and LFA-1 or ICAM-1. The combination of anti-CD3, anti-CD4/CD8, and IL-2 stimulated approximately 20% of CD4+ cells and 30% of CD8+ cells to proliferate. Inclusion of anti-ICAM-1 antibody increased these frequencies to 30 and 40% respectively. Maximum activation frequencies were obtained with the combination of anti-CD3, anti-CD4/CD8, and anti-LFA-1 which stimulated cell division by approximately 40% of single CD4+ cells and at least 60% of single CDB + cells. Under these conditions, 30 - 40% of the resultant CD4+ clones and >90% of CD8+ clones secreted IL-3 and IFN-gamma. In addition to responding at higher frequencies that CD4+ cells, CD8+ cells formed larger clones which produced 4-fold higher levels of both cytokines. Although the expression of IL-2, IL-3, IFN-gamma, granulocyte-macrophage colony stimulating factor and tumor necrosis factor-alpha could be detected in CD4+ and CD8+ clones at the mRNA level following reverse transcription and polymerase chain reaction amplification, neither the secreted nor mRNA expression of IL-4 or IL-6 was detected in any of the tested clones. It is concluded that co-stimulation of T cells via LFA-1 or ICAM-1 can enhance T cell receptor-dependent activation in the absence of accessory cells and that this mode of stimulation leads to the expression of a restricted range of cytokine genes.
Publisher: OXFORD UNIV PRESS UNITED KINGDOM
Keywords: MONOCLONAL-ANTIBODIES; LYMPHOCYTES-T; CROSS-LINKING; INTERLEUKIN-2 PRODUCTION; STIMULATORY FACTOR; ANTIGEN RECEPTOR; KINASE P56LCK; MESSENGER-RNA; GROWTH-FACTOR; LYMPHOKINE
Publisher's Version: https://doi.org/10.1093/intimm/4.4.475
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 1992-04-01 12:00:00