Early-onset age-related changes in dendritic cell subsets can impair antigen-specific T helper 1 (Th1) CD4 T cell priming.
Decline in CD4 T cell immune responses is associated with aging. Although a number of immunological defects have been identified in elderly mice (>18 months old), a key early-onset immune defect at middle age could be a driver or contributor to defective CD4 T cell responses. Our studies demonstrate that age-related alterations in DC subsets within the priming environment of middle-aged mice (12 months old) correlate with and can directly contribute to decreases in antigen-specific CD4 T cell Th1 differentiation, which measured by T-bet and IFN-γ expression, was decreased significantly in T cells following VSV infection or s.c. immunization with a protein antigen in the context of immune stimulation via OX40. The deficient Th1 phenotype, observed following protein antigen challenge, was found to be the result of an age-related decrease in an inflammatory DC subset (CD11b+ Gr-1/Ly6C+) in the dLN that corresponded with T cell dysfunction. In the virus model, we observed significant changes in two DC subsets: mDCs and pDCs. Thus, different, early age-related changes in the DC profile in the priming environment can significantly contribute to impaired Th1 differentiation, depending on the type of immunological challenge.
Departments of Immunology/Microbiology and.
Michelle
M
Farazi
General Surgery, Rush University Medical Center, Chicago, Illinois, USA;
Zachary
Z
Cohn
Rush University Cancer Center, Chicago, Illinois, USA; and.
Justine
J
Nguyen
Providence Portland Medical Center, Earle A. Chiles Research Institute, Portland, Oregon, USA.
Andrew D
AD
Weinberg
Departments of Immunology/Microbiology and General Surgery, Rush University Medical Center, Chicago, Illinois, USA; Rush University Cancer Center, Chicago, Illinois, USA; and carl_ruby@rush.edu.
Carl E
CE
Ruby
D000375:Aging / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D005260:Female; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D053262:Receptors, OX40 / Q000235:genetics / Q000276:immunology; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000098815:T-bet Transcription Factor
D000956:Antigens, Viral; D053262:Receptors, OX40; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C505717:Tnfrsf4 protein, mouse; D007371:Interferon-gamma
OX40; T-bet; aging; vesicular stomatitis virus