Defining the cellular and molecular mechanisms of interaction of developing thymocytes with nonlymphoid cells of the thymic microenvironment is critical for understanding normal thymus function. We have previously shown that the CD2/LFA-3 adhesion pathway is important in the interaction of thymocytes with a variety of LFA-3+ nonlymphoid thymic microenvironment cell types. Moreover, T cell activation via the CD2 (alternative, Ag independent) pathway is considered an important mechanism for intrathymic T cell proliferation. To study the relevance of CD2/LFA-3 interactions to human thymocyte activation, we have used purified LFA-3 Ag in several in vitro assays of thymocyte proliferation. Whereas LFA-3 Ag alone did not induce thymocyte proliferation, LFA-3 Ag in combination with the anti-CD2 antibody, CD2.1, and rIL-2 induced marked thymocyte proliferation. Additionally, the anti-CD28 antibody, Kolt2, could substitute for rIL-2, resulting in thymocyte activation induced by LFA-3 Ag in combination with antibodies CD2.1 and Kolt2. In both triggering systems, LFA-3 induced thymocyte activation was dependent upon the concentration of LFA-3 Ag. LFA-3 Ag-dependent thymocyte activation was directed primarily toward CD1-, mature thymocytes. Finally, intact SRBC that express the sheep homolog of LFA-3, T11TS, in combination with antibody CD2.1 and rIL-2 could also induce thymocyte activation. These data suggest that interaction of LFA-3 molecules with thymocyte CD2 molecules may provide a component of the stimulus for normal intrathymic thymocyte activation leading to thymocyte proliferation.
Publications
Purified lymphocyte function-associated antigen-3 (LFA-3) activates human thymocytes via the CD2 pathway. J. Immunol. 141, 9, 2980-2985 (1988).Abstract
Functional evidence that intercellular adhesion molecule-1 (ICAM-1) is a ligand for LFA-1 in cytotoxic T cell recognition. Eur. J. Immunol. 18, 4, 637-640 (1988).Abstract
The leukocyte adhesion deficiency: Molecular basis and functional consequences. Immunodefic. Rev. 1, 39-54 (1988).
The human leukocyte adhesion glycoprotein Mac-1 (complement receptor type 3, CD11b) α subunit. J. Biol. Chem. 263, 25, 12403-12411 (1988).Abstract
Intercellular adhesion molecule-1 (ICAM-1) is involved in the cytolytic T lymphocyte interaction with human synovial cells. J. Cell. Physiol. 137, 1, 173-178 (1988).Abstract
Adhesion of T lymphoblasts to epidermal keratinocytes is regulated by interferon γ and is mediated by intercellular adhesion molecule-1 (ICAM-1). J. Exp. Med. 167, 4, 1323-1340 (1988).Abstract
ICAM-1 a ligand for LFA-1 dependent adhesion of B, T and myeloid cells. Nature 331, 6151, 86-88 (1988).Abstract
The major Fc receptor in blood has a phosphatidylinositol anchor and is deficient in paroxysmal noctural hemoglobinuria. Nature 333, 6173, 565-567 (1988).Abstract
Biosynthesis and function of LFA-3 in human mutant cells deficient in phosphatidylinositol anchored proteins. J. Immunol. 141, 12, 4283-4290 (1988).Abstract
Purified lymphocyte function-associated antigen-3 and T11 target structure are active in CD2-mediated T cell stimulation. Eur. J. Immunol. 17, 12, 1847-1850 (1987).Abstract
The T lymphocyte glycoprotein CD2 (LFA-2/T11/E-rosette receptor) binds the cell surface ligand LFA-3. Nature 326, 6111, 400-403 (1987).Abstract
Stimulated mobilization of monocyte Mac-1 and p150,95 adhesion proteins from an intracellular vesicular compartment to the cell surface. J. Clin. Invest. 80, 2, 535-544 (1987).Abstract
Biosynthesis and glycosylation of p150,95 and related leukocyte adhesion proteins. J. Immunol. 139, 3, 842-847 (1987).Abstract