Effect of CD4+CD25+ and CD4+CD25- T regulatory cells on the generation of cytolytic T cell response to a self but human tumor-associated epitope in vitro.
CD4+ T cells naturally expressing CD25 molecules (natural T regulatory cells (Tregs)) have a role in maintaining self tolerance and in regulating responses to infectious agents, transplantation Ags, and tumor Ags. CD4+ Tregs induced from CD4+CD25- precursors (induced Tregs) also regulate immune responses in the periphery. However, which of these Tregs is a major impediment in generating antitumor CTL responses is not clear. We show that although the CD4+CD25+ subsets isolated from peripheral blood-derived lymphocytes do suppress the proliferation of CD4+CD25- effector T cells, they do not suppress the activation and expansion of the self but melanoma-associated, melanoma Ag-reactive T cell 1 (MART-1)27-35-specific CD8+ T cells stimulated by the respective peptide-loaded matured dendritic cells in vitro. The CD4+CD25- counterparts, in contrast, lead to the generation of CD25+ glucocorticoid-inducible TNFR+-Forkhead/winged helix transcription factor+ populations and efficiently suppress the activation and expansion of the MART-127-35 epitope-specific CTLs. Our data suggest that when CTL precursors are optimally stimulated, natural Tregs are not a formidable constraint toward generating a robust antitumor CTL response, but induced Tregs could be.
Chattopadhyay
Subhasis
S
University of Connecticut School of Medicine, Farmington Avenue, Farmington, CT 06030, USA.
Mehrotra
Shikhar
S
Chhabra
Arvind
A
Hegde
Upendra
U
Mukherji
Bijay
B
Chakraborty
Nitya G
NG
D000951:Antigens, Neoplasm; D001324:Autoantigens; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008545:Melanoma / Q000276:immunology; D009363:Neoplasm Proteins / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D017634:Self Tolerance; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
D000951:Antigens, Neoplasm; D001324:Autoantigens; D000939:Epitopes; C105787:MART-1-Melan-A(27-35) epitope; D009363:Neoplasm Proteins; D015375:Receptors, Interleukin-2