Circulating immunoglobulin-bound transforming growth factor beta at a late tumour-bearing stage impairs antigen-specific responses of CD4+ T cells.
In order to elucidate the mechanisms by which tumour-specific CD4+ T-cell responses are impaired during tumour development, an attempt was made to identify factors which impair CD4+ T-cell responses at a late tumour-bearing stage. Plasma from mice bearing B16 melanoma for 30 days (plasma d30) showed a more profound immunosuppressive effect on the in vitro proliferation of unrelated antigen-specific CD4+ T cells in the presence of both antigen and antigen-presenting cells (APC) than plasma from naïve mice. The level of plasma transforming growth factor (TGF)- was elevated in mice bearing B16 melanoma for 30 days compared with naïve mice, and the suppressive effect of plasma d30 was partially diminished by the neutralization of TGF-. Interestingly, immunoglobulin (IgG)-bound TGF-, but not IgG-unbound TGF-, in plasma d30 was suggested to be responsible for the immunosuppressive activity. In addition, no suppressive effect of plasma d30 was observed when antigen was added as a class II peptide, thus suggesting that the impaired proliferation of CD4+ T cells in the presence of plasma d30 was due to a dysfunction of antigen uptake/processing by APC. Furthermore, dissociation between IgG and TGF- resulted in a loss of the suppressive activity of plasma d30. Taken together, these results suggest that circulating IgG-bound TGF- is, at least in part, responsible for the impaired responses of CD4+ T cells at the late tumour-bearing stage by suppressing antigen uptake/ processing by APC.
Harada
M
M
Department of Virology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8482, Japan. haramamo@med.kurume-u.ac.jp
Tatsugami
K
K
Nomoto
M
M
Nomoto
K
K
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007165:Immunosuppression Therapy; D008546:Melanoma, Experimental / Q000097:blood / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011485:Protein Binding; D016212:Transforming Growth Factor beta / Q000097:blood / Q000276:immunology*
D000951:Antigens, Neoplasm; D007074:Immunoglobulin G; D016212:Transforming Growth Factor beta