Peptide-stimulated DO11.10 T cells divide well but accumulate poorly in the absence of TLR agonist treatment.
Immunological adjuvants increase the clonal burst size of antigen-specific T cell populations by mechanisms that remain incompletely understood. Using the DO11.10 adoptive transfer system to study peptide-stimulated T cell responses, we found that TLR agonist treatment increased the extent of cellular division undergone by responding T cells, but not by enough to explain the net increases in T cell yield that were achieved. Two novel analyses involving CFSE dye dilution analysis were used to characterize the shortfall, both of which were consistent with the idea that DO11.10 T cells are frequently lost during proliferation unless TLR agonists are present. T cell loss during clonal expansion was correlated with decreased levels of Bcl-2, but TLR agonists did not appear to afford protection by restoring levels of Bcl-2 or of cell surface IL-7Ralpha chain expression. TLR-mediated protection also failed to correlate with increased expression of Bcl-x or decreased expression of pro-apoptotic Bim. Our findings suggest that DO11.10 T cells stimulated by antigenic peptide in vivo divide well, but fail to accumulate efficiently unless TLR agonists are present.
Thompson
Bruce S
BS
Institute for Cellular Therapeutics, Department of Microbiology and Immunology, University of Louisville Medical School, Louisville, KY, USA.
Mata-Haro
Veronica
V
Casella
Carolyn R
CR
Mitchell
Thomas C
TC
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D002449:Cell Aggregation / Q000235:genetics / Q000276:immunology*; D002453:Cell Cycle / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology*; D019070:Cell Lineage / Q000235:genetics / Q000502:physiology; D002999:Clone Cells; D008221:Lymphoid Tissue / Q000166:cytology; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010455:Peptides / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000166:cytology*; D051193:Toll-Like Receptors / Q000819:agonists* / Q000502:physiology*
D010455:Peptides; D019253:Proto-Oncogene Proteins c-bcl-2; D020395:Receptors, Interleukin-7; D051193:Toll-Like Receptors; C415350:interleukin-7 receptor, alpha chain