Age related changes in Fas (CD95) and Fas ligand gene expression and cytokine profiles in healthy Indians.
Ageing in human and animal models show changes in many aspects of protective immunity, particularly lymphopoenia and progressive decline in immune functions leading to increased frequency of infection and neoplasia. However, the exact mechanism of these defects is still unclear. In this study, elderly subjects showed a decline in CD3+ and CD4+ T-cell subsets as well as serum IL-2 levels. Serum IL-6 was significantly raised while expression of its signaling receptor gp130 was significantly impaired in elderly as compared to the younger ones. Additionally, all the elderly individuals showed constitutive expression of Fas and FasL mRNA; however, none of the younger individuals expressed mRNA transcripts constitutively although induced expression was seen in both the groups. Similarly, frequency of Fas and FasL expressing CD4+ and CD8+ T-cell subsets were significantly (p < 0.001) higher in elderly subjects as compared to the younger ones. Elderly individuals also showed a significantly (p < 0.001) higher frequency of activation induced cell death (AICD). Since interaction of Fas with its cognate ligand (FasL) activates death inducing caspases leading to apoptosis, and gp130 induces anti-apoptotic signal through STAT-3 pathway, these results suggest that the decline in protective immune functions in aged individuals may be related to Fas and FasL mediated apoptosis of peripheral T-cell subsets.
Sawhney
Meenakshi
M
Tumour and Molecular Immunology Laboratory, Department of Biotechnology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi-110029, India.
Mathew
Mary
M
Valarmathi
Mani T
MT
Das
Satya N
SN
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D050822:Cytokine Receptor gp130 / Q000097:blood; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology*; D020869:Gene Expression Profiling; D006801:Humans; D016130:Immunophenotyping; D007194:India; D007376:Interleukin-2 / Q000097:blood; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology; D019014:fas Receptor / Q000378:metabolism*
D017252:CD3 Complex; D016207:Cytokines; D053222:Fas Ligand Protein; C494199:IL6ST protein, human; D007376:Interleukin-2; D012333:RNA, Messenger; D019014:fas Receptor; D050822:Cytokine Receptor gp130