Abstract
Although immunosuppression has long been recognized in Hodgkin lymphoma (HL), the underlying basis for the lack of an effective immune response against the tumor remains unclear. The aim was to test our hypothesis that regulatory T cells dominate involved lymph nodes. The approach was to assay CD4(+) T-cell function in HL-infiltrating lymphocytes (HLILs) and paired peripheral blood mononuclear cells (PBMCs) of 24 patients. Strikingly, unlike PBMCs, HLILs were anergic to stimulation with mitogen, primary, or recall antigens, mounting no proliferative responses and only rare T-helper 1 (Th1) or Th2 cytokine responses. Mixing paired HLILs and PBMCs showed the anergic effect was dominant and suppressed PBMC responses. Furthermore, flow cytometry demonstrated that HLILs contained large populations of both interleukin-10 (IL-10)-secreting T-regulatory 1 (Tr1) and CD4(+)CD25(+) regulatory T cells. We found evidence for 3 mechanisms of action implicated in the suppressive functions of regulatory T cells: the inhibition of PBMCs by HLILs was ameliorated by neutralizing IL-10, by preventing cell-to-cell contact, and by blocking anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4). Thus, HLILs are highly enriched for regulatory T cells, which induce a profoundly immunosuppressive environment and so provide an explanation for the ineffective immune clearance of Hodgkin-Reed Sternberg cells. (C) 2004 by The American Society of Hematology.
| Original language | English |
|---|---|
| Pages (from-to) | 1755-1762 |
| Number of pages | 7 |
| Journal | Blood |
| Volume | 103 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Mar 2004 |
Keywords
- REED-STERNBERG CELLS
- VERSUS-HOST DISEASE
- INTERLEUKIN-13 RECEPTOR
- IMMUNE-RESPONSES
- PERIPHERAL-BLOOD
- TUMOR-CELLS
- EXPRESSION
- EBV
- CYTOKINES
- CYCLOPHOSPHAMIDE
Cite this
Immunosuppressive regulatory T cells are abundant in the reactive lymphocytes of Hodgkin lymphoma. / Marshall, Neil Andrew; Christie, L. E.; Munro, Laura R; Culligan, D. J.; Johnston, Peter W.; Barker, Robert Norman; Vickers, Mark Adrian.
In: Blood, Vol. 103, No. 5, 03.2004, p. 1755-1762.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Immunosuppressive regulatory T cells are abundant in the reactive lymphocytes of Hodgkin lymphoma
AU - Marshall, Neil Andrew
AU - Christie, L. E.
AU - Munro, Laura R
AU - Culligan, D. J.
AU - Johnston, Peter W.
AU - Barker, Robert Norman
AU - Vickers, Mark Adrian
PY - 2004/3
Y1 - 2004/3
N2 - Although immunosuppression has long been recognized in Hodgkin lymphoma (HL), the underlying basis for the lack of an effective immune response against the tumor remains unclear. The aim was to test our hypothesis that regulatory T cells dominate involved lymph nodes. The approach was to assay CD4(+) T-cell function in HL-infiltrating lymphocytes (HLILs) and paired peripheral blood mononuclear cells (PBMCs) of 24 patients. Strikingly, unlike PBMCs, HLILs were anergic to stimulation with mitogen, primary, or recall antigens, mounting no proliferative responses and only rare T-helper 1 (Th1) or Th2 cytokine responses. Mixing paired HLILs and PBMCs showed the anergic effect was dominant and suppressed PBMC responses. Furthermore, flow cytometry demonstrated that HLILs contained large populations of both interleukin-10 (IL-10)-secreting T-regulatory 1 (Tr1) and CD4(+)CD25(+) regulatory T cells. We found evidence for 3 mechanisms of action implicated in the suppressive functions of regulatory T cells: the inhibition of PBMCs by HLILs was ameliorated by neutralizing IL-10, by preventing cell-to-cell contact, and by blocking anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4). Thus, HLILs are highly enriched for regulatory T cells, which induce a profoundly immunosuppressive environment and so provide an explanation for the ineffective immune clearance of Hodgkin-Reed Sternberg cells. (C) 2004 by The American Society of Hematology.
AB - Although immunosuppression has long been recognized in Hodgkin lymphoma (HL), the underlying basis for the lack of an effective immune response against the tumor remains unclear. The aim was to test our hypothesis that regulatory T cells dominate involved lymph nodes. The approach was to assay CD4(+) T-cell function in HL-infiltrating lymphocytes (HLILs) and paired peripheral blood mononuclear cells (PBMCs) of 24 patients. Strikingly, unlike PBMCs, HLILs were anergic to stimulation with mitogen, primary, or recall antigens, mounting no proliferative responses and only rare T-helper 1 (Th1) or Th2 cytokine responses. Mixing paired HLILs and PBMCs showed the anergic effect was dominant and suppressed PBMC responses. Furthermore, flow cytometry demonstrated that HLILs contained large populations of both interleukin-10 (IL-10)-secreting T-regulatory 1 (Tr1) and CD4(+)CD25(+) regulatory T cells. We found evidence for 3 mechanisms of action implicated in the suppressive functions of regulatory T cells: the inhibition of PBMCs by HLILs was ameliorated by neutralizing IL-10, by preventing cell-to-cell contact, and by blocking anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4). Thus, HLILs are highly enriched for regulatory T cells, which induce a profoundly immunosuppressive environment and so provide an explanation for the ineffective immune clearance of Hodgkin-Reed Sternberg cells. (C) 2004 by The American Society of Hematology.
KW - REED-STERNBERG CELLS
KW - VERSUS-HOST DISEASE
KW - INTERLEUKIN-13 RECEPTOR
KW - IMMUNE-RESPONSES
KW - PERIPHERAL-BLOOD
KW - TUMOR-CELLS
KW - EXPRESSION
KW - EBV
KW - CYTOKINES
KW - CYCLOPHOSPHAMIDE
U2 - 10.1182/blood-2003-07-2594
DO - 10.1182/blood-2003-07-2594
M3 - Article
VL - 103
SP - 1755
EP - 1762
JO - Blood
JF - Blood
SN - 0006-4971
IS - 5
ER -