Proliferative capacity of senescent lymphocytes. II. Monoclonal antibody stimulation of mucosal and systemic lymphocytes via T cell activation molecules, CD3 epsilon, T cell receptor V beta 8 chain, and phosphatidylinositol-linked anchored receptors THY-1 and LY-6A.2/TAP.
The proliferative capacity of senescent mucosal and systemic lymphocytes was studied in response to monoclonal antibody (Mab) stimulation of T cell activation molecules, CD3 epsilon, V beta 8a chain of the T cell receptor (TcR-V beta 8), Thy-1, and Ly-6A.2/TAP. The percentage of positive cells, fluorescence intensities, and proliferative responses of lymphocytes from the spleen and mesenteric lymph nodes (mln) of individual C57BL/6J male mice were compared at 2, 4, 12, 20, and 30 months of age. Mabs F23.1, 145-C11, Jij.10, and D7 were used to measure TCR-V beta 8a, CD3 epsilon, Thy-1, and Ly6A.2/TAP expressions, respectively. Optimal dose and kinetic studies were determined. There were no significant age-related changes in the percentage of splenic cells expressing CD3 epsilon, TCR-V beta 8a, Thy-1, and Ly6A.2, as well as their fluorescence intensities on the cell surface as measured flow cytometry. For mln cells, the percentage of cells expressing TCR-V beta 8a, Thy-1, and Ly6A.2 did not significantly change with age. A significant age-related increase was found in the percentage of mln cells expressing CD3 epsilon. The fluorescence intensities of CD3 epsilon, TCR-V beta 8a, and Ly6A.2 expression on the cell surface of mln cells significantly increased with age. Mabs anti-TcR-V beta 8a and anti-CD3 epsilon stimulation of splenic lymphocytes in culture for 3 days revealed a significant decline in proliferative responses after 12 months of age. When splenic cells were stimulated with Mab anti-CD3 epsilon in combination with optimal doses of phorbol myristate acetate (PMA) in culture for 3 days, there was a two-fold elevation in the proliferative response with a significant decline occurring after 20 months of age. Mab anti-TcR-V beta 8a and Mab anti-CD3 epsilon plus PMA stimulation of mln lymphocytes consistently revealed a significant decline in proliferative responses only after 20 months of age. Both splenic and mln cells showed a significant decline in proliferative responses to Mab anti-Thy-1 stimulation after 12 months of age. There was no age-related change in the proliferation of splenic and mln cells to Mab anti-Ly6A.2 activation. These results indicate that the onset and rate of age-related decline in the proliferative capacity of lymphocytes after stimulation with Mabs anti-CD3 epsilon and anti-TcR-V beta 8 chain changes much later and slower in the mln than those of the spleen.(ABSTRACT TRUNCATED AT 400 WORDS)
Green-Johnson
J M
JM
Department of Microbiology and Immunology, Queen's University, Kingston, Ontario, Canada.
Szewczuk
M R
MR
D000375:Aging / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D000954:Antigens, Surface; D017252:CD3 Complex; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D010716:Phosphatidylinositols / Q000276:immunology; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013601:T-Lymphocytes / Q000276:immunology*; D018800:Thy-1 Antigens
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D000954:Antigens, Surface; D017252:CD3 Complex; D010716:Phosphatidylinositols; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018800:Thy-1 Antigens