CD4 T cell defects in the aged: causes, consequences and strategies to circumvent.
Aging leads to reduced immunity, especially adaptive responses. A key deficiency is the poor ability to mount robust antibody response. Although intrinsic alterations in B cells with age are in part responsible, impaired CD4 T cell help makes a major contribution to the poor antibody response. Other CD4 effector responses and memory generation are also impaired. We find delayed and reduced development of CD4 T follicular help (Tfh) cells in aged mice in response to influenza infection with reduction of long-lived plasma cells. When we examine CD4 subsets we also find a shift towards Th1 and cytotoxic CD4 (ThCTL) responses. We summarize strategies to circumvent the CD4 T cell defect in aged, including adjuvants and proinflammatory cytokines. We find that we can strongly enhance responses of aged naïve CD4 T cells by using Toll-like receptor (TLR) activated dendritic cells (DC) as APC in vivo and that this leads to improved germinal center B cells and IgG antibody responses. The enhanced response of aged naïve CD4 T cells is dependent on IL-6 produced by the DC.
Department of Pathology, University of Massachusetts Medical School, USA.
Wenliang
W
Zhang
Department of Pathology, University of Massachusetts Medical School, USA.
Vinayak
V
Brahmakshatriya
Department of Pathology, University of Massachusetts Medical School, USA. Electronic address: Susan.Swain@umassmed.edu.
Susan L
SL
Swain
D056704:Adaptive Immunity / Q000502:physiology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000368:Aged; D000375:Aging / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism / Q000502:physiology; D051379:Mice; D016176:T-Lymphocyte Subsets / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology
D000276:Adjuvants, Immunologic; D016207:Cytokines; D015850:Interleukin-6
Ab production; Aging; CD4 T cell help; CD4 T cells; IL-6