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.
Department of Pathology, Columbia University, New York, NY 10032, USA.
Seunghee
S
Kim-Schulze
Luigi
L
Scotto
George
G
Vlad
Flavia
F
Piazza
Hana
H
Lin
Zhuoru
Z
Liu
Raffaello
R
Cortesini
Nicole
N
Suciu-Foca
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