Recombinant Ig-like transcript 3-Fc modulates T cell responses via induction of Th anergy and differentiation of CD8+ T suppressor cells.
The Ig-like transcript (ILT)3 is crucial to the tolerogenic activity acquired by dendritic cells exposed to allospecific T suppressor (Ts) cells. We have explored the immunomodulatory property of the extracellular region of ILT3 using a cytoplasmic deletion mutant of ILT3 (ILT3delta), expressed as membrane-bound ILT3 on KG1 cells, and a rILT3-Fc fusion protein. We found that both membrane-bound and soluble ILT3 inhibited T cell proliferation in primary and secondary MLC inducing anergy in CD4+ Th cells and suppressing the differentiation of IFN-gamma-producing CD8+ CTL. Furthermore, membrane-bound and soluble ILT3 induced the differentiation of CD8+ FOXP3+ Ts cells in primary 7-day MLC. The suppressive activity of these CD8+ Ts cells is alloantigen specific and mediated by their capacity to induce the up-regulation of ILT3 and down-regulation of costimulatory molecules such as CD86 in APC from the stimulator used for priming, but not on control HLA-mismatched APC. Our finding that ILT3-Fc has potent immunosuppressive activity in vitro and that it acts on T cells only upon activation suggests the possibility that this agent may be of use for specific suppression of the immune response in autoimmunity or transplantation.
Kim-Schulze
Seunghee
S
Department of Pathology, Columbia University, New York, NY 10032, USA.
Scotto
Luigi
L
Vlad
George
G
Piazza
Flavia
F
Lin
Hana
H
Liu
Zhuoru
Z
Cortesini
Raffaello
R
Suciu-Foca
Nicole
N
D002454:Cell Differentiation / Q000276:immunology*; D002460:Cell Line; D017635:Clonal Anergy / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000502:physiology*; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D011971:Receptors, Immunologic; D011994:Recombinant Proteins / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism
D051858:Forkhead Transcription Factors; D007141:Immunoglobulin Fc Fragments; C107907:LILRB4 protein, human; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D011994:Recombinant Proteins