Cellular autoreactivity against heat shock protein 60 in renal transplant patients: peripheral and graft-infiltrating responses.
Autoreactivity to heat shock protein 60 (Hsp60) has been implicated in the pathogenesis and regulation of chronic inflammation, especially in autoimmune diseases. In transplantation, there is a lack of information regarding the cytokine profile and specificity of cells that recognize self-Hsp60 as well as the kinetics of autoreactivity following transplantation. We studied the cellular reactivity of peripheral and graft-infiltrating lymphocytes against Hsp60 in renal transplant patients. Cytokine production induced by this protein in peripheral blood mononuclear cells indicated a predominance of interleukin (IL)-10 during the late post-transplantation period, mainly in response to intermediate and C-terminal peptides. Patients with chronic rejection presented reactivity to Hsp60 with a higher IL-10/interferon (IFN)-gamma ratio compared to long-term clinically stable patients. Graft-infiltrating T cell lines, cocultured with antigen-presenting cells, preferentially produced IL-10 after Hsp60 stimulation. These results suggest that, besides its proinflammatory activity, autoreactivity to Hsp60 in transplantation may also have a regulatory role.
Caldas
C
C
Heart Institute (InCor), University of São Paulo Medical School, São Paulo, SP, Brazil.
Luna
E
E
Spadafora-Ferreira
M
M
Porto
G
G
Iwai
L K
LK
Oshiro
S E
SE
Monteiro
S M
SM
Fonseca
J A
JA
Lemos
F
F
Hammer
J
J
Ho
P L
PL
Kalil
J
J
Coelho
V
V
D000293:Adolescent; D000328:Adult; D015551:Autoimmunity; D002460:Cell Line; D018834:Chaperonin 60 / Q000276:immunology*; D002648:Child; D002908:Chronic Disease; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007668:Kidney / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology*; D008875:Middle Aged; D011184:Postoperative Period; D016176:T-Lymphocyte Subsets / Q000276:immunology
D018834:Chaperonin 60; D016753:Interleukin-10; D007371:Interferon-gamma