Impaired antigen-induced CD8+ T cell clonal expansion in aging is due to defects in antigen presenting cell function.
CD8+ T cell activation depends on interaction with antigen-presenting cells (APCs) and this interaction leads to the expansion of T cells with the capacity to control infection. Using professional APCs, we demonstrate that with age, the duration of APC-T cell contact time required to achieve clonal expansion increases. Naïve CD8+ T cells from aged mice showed no defect in antigen-induced proliferation when stimulated with APC from young mice. In contrast, CD8+ T cells from young mice exhibited reduced clonal expansion and secreted significantly lower amounts of IFN-gamma when stimulated by APCs from aged mice. The aged APCs were defective in costimulatory molecule expression and cytokine and chemokine secretion. These data indicate that defects in APC function lead to poor T cell clonal expansion and function in aging.
Plowden
Julie
J
Influenza Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Renshaw-Hoelscher
Mary
M
Gangappa
Shivaprakash
S
Engleman
Carrie
C
Katz
Jacqueline M
JM
Sambhara
Suryaprakash
S
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D016922:Cellular Senescence / Q000276:immunology; D002999:Clone Cells / Q000166:cytology / Q000276:immunology; D018899:CpG Islands / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000276:immunology; D019041:L-Selectin / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013864:Thioglycolates / Q000494:pharmacology
D016207:Cytokines; D011948:Receptors, Antigen, T-Cell; D013864:Thioglycolates; D019041:L-Selectin; D007371:Interferon-gamma