During normal aging and in chronic diabetes the excessive accumulation of reactive glucose-protein or glucose-lipid adducts known as advanced glycosylation endproducts (AGEs) has been shown to induce tissue dysfunction, in part through interaction with AGE-specific receptors on monocyte/macrophages and other cells. Recognizing that circulating lymphocytes trafficking through tissues interact with tissue AGEs, we searched for the expression of AGE-binding sites on peripheral blood T lymphocytes. Resting rat and human T cells bound 125I-AGE-albumin with an affinity of 7.8 x 10(7) M-1, whereas, after stimulation with phytohemagglutinin (PHA) for 48 h, binding affinity increased to 5.8 x 10(8) M-1. Flow cytometric analysis of resting rat T cells using polyclonal antibodies raised against rat liver AGE-binding proteins (p60 and p90) revealed the constitutive expression of both immunoreactivities. The number of resting CD4+ and CD8+ T cells positive for anti-p60 antibody binding (34.2 and 58.5%, respectively) increased to 92 and 90% of cells after 48-h stimulation with PHA. Exposure of PHA-activated T lymphocytes to AGE-albumin enhanced expression of interferon gamma (IFN-gamma) mRNA 10-fold and induced greater elaboration of the mature protein than did exposure to unmodified protein or PHA treatment alone. These data indicate that T cells contain an inducible system of surface receptors for AGE-modified proteins, and that receptor occupancy is linked to lymphokine production. This T cell AGE-receptor system might serve to target lymphocytes to AGE-rich tissues and involve them in the regulation of tissue homeostasis either by assisting in macrophage-dependent clearance of AGE-proteins, or by exerting direct antiproliferative action on mesenchymal cells. Under conditions of excessive AGE-protein and AGE lipid accumulation (e.g., aging and diabetes), enhanced production of AGE-induced IFN-gamma may accelerate immune responses that contribute to tissue injury.
Skip Nav Destination
Article navigation
1 December 1993
Article|
December 01 1993
Advanced glycosylation endproduct-specific receptors on human and rat T-lymphocytes mediate synthesis of interferon gamma: role in tissue remodeling.
F Imani,
F Imani
Picower Institute for Medical Research, Manhasset, New York 11030.
Search for other works by this author on:
Y Horii,
Y Horii
Picower Institute for Medical Research, Manhasset, New York 11030.
Search for other works by this author on:
M Suthanthiran,
M Suthanthiran
Picower Institute for Medical Research, Manhasset, New York 11030.
Search for other works by this author on:
E Y Skolnik,
E Y Skolnik
Picower Institute for Medical Research, Manhasset, New York 11030.
Search for other works by this author on:
Z Makita,
Z Makita
Picower Institute for Medical Research, Manhasset, New York 11030.
Search for other works by this author on:
V Sharma,
V Sharma
Picower Institute for Medical Research, Manhasset, New York 11030.
Search for other works by this author on:
P Sehajpal,
P Sehajpal
Picower Institute for Medical Research, Manhasset, New York 11030.
Search for other works by this author on:
H Vlassara
H Vlassara
Picower Institute for Medical Research, Manhasset, New York 11030.
Search for other works by this author on:
F Imani
Picower Institute for Medical Research, Manhasset, New York 11030.
Y Horii
Picower Institute for Medical Research, Manhasset, New York 11030.
M Suthanthiran
Picower Institute for Medical Research, Manhasset, New York 11030.
E Y Skolnik
Picower Institute for Medical Research, Manhasset, New York 11030.
Z Makita
Picower Institute for Medical Research, Manhasset, New York 11030.
V Sharma
Picower Institute for Medical Research, Manhasset, New York 11030.
P Sehajpal
Picower Institute for Medical Research, Manhasset, New York 11030.
H Vlassara
Picower Institute for Medical Research, Manhasset, New York 11030.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1993) 178 (6): 2165–2172.
Citation
F Imani, Y Horii, M Suthanthiran, E Y Skolnik, Z Makita, V Sharma, P Sehajpal, H Vlassara; Advanced glycosylation endproduct-specific receptors on human and rat T-lymphocytes mediate synthesis of interferon gamma: role in tissue remodeling.. J Exp Med 1 December 1993; 178 (6): 2165–2172. doi: https://doi.org/10.1084/jem.178.6.2165
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionSuggested Content
Email alerts
Advertisement