Attenuation of CD8(+) T-cell function by CD4(+)CD25(+) regulatory T cells in B-cell non-Hodgkin's lymphoma.
The underlying mechanisms by which tumor cells are resistant to CTL-mediated apoptosis are not clear. Using a human model of B-cell non-Hodgkin's lymphoma (B-cell NHL), we show that intratumoral T(reg) cells inhibit the proliferation and granule production of activated autologous infiltrating CD8(+) T cells. Our results also show that degranulation and subsequent cytotoxic activity of infiltrating CD8(+) T cells exposed to lymphoma B cells is completely attenuated by the presence of intratumoral T(reg) cells. Furthermore, we show that increased numbers of intratumoral T(reg) cells correlates with the number of CD8(+) T cells in biopsy specimens from patients with B-cell NHL, supporting the in vitro findings that intratumoral T(reg) cells inhibit proliferation of infiltrating CD8(+) T cells. Taken together, these data indicate that human lymphoma B cells are sensitive to autologous CTL-mediated cell death but are protected by the inhibitory function of intratumoral T(reg) cells.
Yang
Zhi-Zhang
ZZ
Division of Hematology and Internal Medicine, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
Novak
Anne J
AJ
Ziesmer
Steven C
SC
Witzig
Thomas E
TE
Ansell
Stephen M
SM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015550:Cell Degranulation / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000276:immunology; D053804:Granzymes / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000096:biosynthesis / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes