PMID- 9507214
OWN - NLM
STAT- MEDLINE
DCOM- 19980421
LR  - 20191211
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 53
IP  - 3
DP  - 1998 Mar
TI  - Interferon-gamma-treated renal tubular epithelial cells induce allospecific 
      tolerance.
PG  - 679-89
AB  - Following organ transplantation, tissue parenchymal cells commonly express major 
      histocompatibility complex (MHC) class II molecules as a result of local cytokine 
      release, and thus acquire the capacity to present donor MHC alloantigens to 
      alloreactive CD4+ T cells. The consequences of such a presentation are likely to 
      be relevant in the induction of tolerance to the transplanted tissues, and this 
      has been reported in animal models of transplantation and in humans. In this 
      study, the consequences of antigen presentation by interferon-gamma 
      (IFN-gamma)-treated human renal tubular epithelial cells (RTEC) to resting and 
      activated CD4+ T cells were investigated. Allogeneic RTEC were unable to 
      stimulate proliferation by peripheral blood CD45 RA+ or RO+ CD4+ T cells from 
      three HLA-mismatched responders. The response to RTEC was partially reconstituted 
      by the addition of murine L cell transfectants expressing human B7.1 (DAP.3-B7), 
      suggesting that the failure of RTEC to stimulate a primary alloresponse was due, 
      at least in part, to a lack of costimulation. T cell clones dependent on 
      B7-mediated co-stimulation also did not respond to peptide presented by RTEC. 
      Most importantly, this lack of reactivity was accompanied by the induction of 
      nonresponsiveness. Incubation with allogeneic, DR-expressing RTEC induced 
      allospecific hyporesponsiveness in both CD45RA+ and RO+ cells. Similarly, 
      overnight incubation with antigen-pulsed RTEC induced nonresponsiveness in the 
      B7-dependent T cell clones. These results suggest that MHC class II expression on 
      RTEC may contribute to the induction of an allospecific nonresponsiveness 
      following organ transplantation.
FAU - Frasca, L
AU  - Frasca L
AD  - Department of Immunology, Royal Postgraduate Medical School, London, England, 
      United Kingdom.
FAU - Marelli-Berg, F
AU  - Marelli-Berg F
FAU - Imami, N
AU  - Imami N
FAU - Potolicchio, I
AU  - Potolicchio I
FAU - Carmichael, P
AU  - Carmichael P
FAU - Lombardi, G
AU  - Lombardi G
FAU - Lechler, R
AU  - Lechler R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (B7-1 Antigen)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Isoantigens)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.1.3.48 (Leukocyte Common Antigens)
SB  - IM
MH  - Animals
MH  - Antigen Presentation
MH  - B7-1 Antigen/genetics
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - Cell Line
MH  - Epithelial Cells/drug effects/immunology
MH  - Histocompatibility Antigens Class II/metabolism
MH  - Humans
MH  - Immune Tolerance/*drug effects
MH  - Interferon-gamma/*pharmacology
MH  - Isoantigens/metabolism
MH  - Kidney Tubules/cytology/*drug effects/*immunology
MH  - L Cells
MH  - Leukocyte Common Antigens/metabolism
MH  - Mice
MH  - Transfection
MH  - Transplantation Immunology
EDAT- 1998/03/21 00:00
MHDA- 1998/03/21 00:01
CRDT- 1998/03/21 00:00
PHST- 1998/03/21 00:00 [pubmed]
PHST- 1998/03/21 00:01 [medline]
PHST- 1998/03/21 00:00 [entrez]
AID - S0085-2538(15)60444-6 [pii]
AID - 10.1046/j.1523-1755.1998.00800.x [doi]
PST - ppublish
SO  - Kidney Int. 1998 Mar;53(3):679-89. doi: 10.1046/j.1523-1755.1998.00800.x.