Increased IL-21 secretion by aged CD4+T cells is associated with prolonged STAT-4 activation and CMV seropositivity.
Advancing age leads to significant decline in immune functions. IL-21 is produced primarily by T follicular helper (Tfh) cells and is required for effective immune cell functions. Here we compared the induction of IL-21 in aged and young subjects. Our investigation demonstrates that CD4+T cells from healthy elderly individuals (age ≥ 65) secreted significantly higher levels of IL-21 on priming with aged and young dendritic cells (DC). Though the aged and young DCs secreted comparable levels of IL-12 on stimulation with anti-CD40 antibody and LPS, culture of DCs with aged CD4+ T cells resulted in increased production of IL-21 as compared to that with young CD4+ T cells. Further examination revealed that the response of aged naïve CD4+ T cells to IL-12 was altered, resulting in increased differentiation of aged Th cells towards Tfh cells. Investigation into the signaling mechanism suggested that phosphorylation of STAT-4 in response to IL-12 was sustained for a longer duration in aged CD4+ T cells as compared to CD4+ T cells from young subjects. Additional analysis demonstrated that increased IL-21 secretion correlated with chronic CMV infection in aged subjects. These findings indicate that chronic CMV infection alters the response of aged CD4+ T cells to IL-12 resulting in an increased secretion of IL-21 and that aging affects Tfh cell responses in humans which may contribute to age-associated inflammation and immune dysfunctions.
Department of Medicine, Division of Basic and Clinical Immunology, University of California, Irvine, CA 92617, USA. aagrawal@uci.edu
Anshu
A
Agrawal
Houfen
H
Su
Justine
J
Chen
Kathryn
K
Osann
Sudhanshu
S
Agrawal
Sudhir
S
Gupta
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003586:Cytomegalovirus Infections / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D004789:Enzyme Activation / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D050797:STAT4 Transcription Factor / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult; D000098546:Interleukin-21
D007378:Interleukins; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D000098546:Interleukin-21