In vitro suppression of xenoimmune-mediated macrophage activation by human CD4+CD25+ regulatory T cells.
BACKGROUND
Macrophages are important effector cells in T cell-mediated xenograft rejection. The aim of this study was to determine whether CD4+CD25+ regulatory T cells (Tregs) were capable of suppressing macrophage activation in vitro.


METHODS
Porcine cell or xenoantigen-primed human peripheral blood mononuclear cells, CD4+ T cell-depleted peripheral blood mononuclear cells, or CD14+ macrophages plus autologous CD4+CD25- T cells were cultured with or without expanded autologous Tregs. Transwell cultures were used to separate the various components to determine the need for cell-cell contact.


RESULTS
Pig cell primed CD14+ macrophages required the presence of CD4+CD25- T cells for activation and increased expression of CD40, interleukin-12, and tumor necrosis factor-alpha. This up-regulated expression of macrophage activation markers was reduced substantially in the presence of autologous Tregs. Coculture with Tregs did not alter macrophage viability but reduced the capacity of macrophages to stimulate proliferation of responder T cells. Tregs required direct contact with CD4+CD25- T cells to inhibit macrophage activation but activated macrophage phenotype was not altered by separating the stimulated human peripheral blood mononuclear cells or CD14+ macrophages from Tregs in a transwell system. Macrophages did not require direct cell contact with porcine stimulator cells for full activation by CD4+CD25- T cells.


CONCLUSIONS
Human Tregs were able to suppress xenoantigen-primed and CD4+ T-cell-mediated macrophage activation and antigen-presenting cell function. However, Tregs had no direct effect on macrophages in vitro.
Fu
Yiling
Y
Center for Transplant and Renal Research, Westmead Millennium Institute, Westmead Hospital, Westmead, 2145 NSW, Australia.
Yi
Shounan
S
Wu
Jingjing
J
Jimenez
Elvira
E
Simond
Denbigh
D
Hawthorne
Wayne J
WJ
O'Connell
Philip J
PJ
D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D015478:Antigens, Heterophile / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D002470:Cell Survival; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D014183:Transplantation, Heterologous / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015478:Antigens, Heterophile; D015704:CD4 Antigens; D053645:Interleukin-2 Receptor alpha Subunit