Agonistic anti-4-1BB antibody promotes the expansion of natural regulatory T cells while maintaining Foxp3 expression.
The engagement of the 4-1BB (CD137) co-stimulatory pathway promotes the activation and proliferation of conventional CD4(+) T and CD8(+) T cells, but the role of 4-1BB co-stimulation in CD4(+) CD25(+) regulatory T cells (Treg) is less clear. In particular, whether 4-1BB stimulation affects the expression of Foxp3, a master gene for Treg, is unknown. This study demonstrates that co-stimulation of 4-1BB engaged by an agonistic antibody promotes the proliferation of Treg in a dependent manner of low-concentration interleukin-2 in vitro. The 4-1BB-expanded Treg maintain Foxp3 expression and their ability to suppress conventional CD4(+) T cells and their feature to produce no interleukin-2. However, the 4-1BB-expanded Treg produce increased levels of interferon-gamma, whose significance is unknown. Thus, 4-1BB co-stimulation plays a role in the expansion of functional CD4(+) CD25(+) Treg cells without adversely affecting their suppressive activity.
Zhang
P
P
Institute of Immunology, Shandong University Medical School, Jinan, Shandong, China.
Gao
F
F
Wang
Q
Q
Wang
X
X
Zhu
F
F
Ma
C
C
Sun
W
W
Zhang
L
L
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000819:agonists / Q000276:immunology*
D000911:Antibodies, Monoclonal; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D012313:RNA; D007371:Interferon-gamma