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Tumor-induced expansion of regulatory T cells by conversion of CD4+CD25- lymphocytes is thymus and proliferation independent.
Cancer Res 2006; 66(8):4488-95CR

Abstract

The CD25- and CD25+ CD4 T-lymphocyte compartments are tightly regulated. We show here that tumors break such balance, increasing the number of CD4+CD25+ T cells in draining lymph node and spleen but not contralateral node of tumor-bearing mice. Tumor injection in thymectomized and CD25-depleted mice shows that CD4+CD25+ T-cell expansion occurs even in the absence of the thymus and independently from proliferation of preexisting CD25+ T cells. These newly generated cells are bona fide regulatory T cells (T reg) in terms of Foxp3 expression and suppression of CD3-stimulated or allogeneic effector cell proliferation. Transfer of congenic Thy1.1 CD4+CD25- T cells, from mice treated or not with vinblastine, into tumor-bearing or tumor-free mice and analysis of recovered donor lymphocytes indicate that conversion is the main mechanism for acquiring the expression of CD25 and Foxp3 through a process that does not require proliferation. Although conversion of CD4+CD25- T cells for generation of T regs has been described as a natural process that maintains peripheral T-reg population, this process is used by the tumor for immune escape. The prompt recovery of T regs from monoclonal antibody-mediated CD25 depletion in tumor-bearing mice suggests attempts able to inactivate rather than deplete them when treating existing tumors.

Authors+Show Affiliations

Immunotherapy and Gene Therapy Unit, Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16618776

Citation

Valzasina, Barbara, et al. "Tumor-induced Expansion of Regulatory T Cells By Conversion of CD4+CD25- Lymphocytes Is Thymus and Proliferation Independent." Cancer Research, vol. 66, no. 8, 2006, pp. 4488-95.
Valzasina B, Piconese S, Guiducci C, et al. Tumor-induced expansion of regulatory T cells by conversion of CD4+CD25- lymphocytes is thymus and proliferation independent. Cancer Res. 2006;66(8):4488-95.
Valzasina, B., Piconese, S., Guiducci, C., & Colombo, M. P. (2006). Tumor-induced expansion of regulatory T cells by conversion of CD4+CD25- lymphocytes is thymus and proliferation independent. Cancer Research, 66(8), pp. 4488-95.
Valzasina B, et al. Tumor-induced Expansion of Regulatory T Cells By Conversion of CD4+CD25- Lymphocytes Is Thymus and Proliferation Independent. Cancer Res. 2006 Apr 15;66(8):4488-95. PubMed PMID: 16618776.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tumor-induced expansion of regulatory T cells by conversion of CD4+CD25- lymphocytes is thymus and proliferation independent. AU - Valzasina,Barbara, AU - Piconese,Silvia, AU - Guiducci,Cristiana, AU - Colombo,Mario P, PY - 2006/4/19/pubmed PY - 2006/6/8/medline PY - 2006/4/19/entrez SP - 4488 EP - 95 JF - Cancer research JO - Cancer Res. VL - 66 IS - 8 N2 - The CD25- and CD25+ CD4 T-lymphocyte compartments are tightly regulated. We show here that tumors break such balance, increasing the number of CD4+CD25+ T cells in draining lymph node and spleen but not contralateral node of tumor-bearing mice. Tumor injection in thymectomized and CD25-depleted mice shows that CD4+CD25+ T-cell expansion occurs even in the absence of the thymus and independently from proliferation of preexisting CD25+ T cells. These newly generated cells are bona fide regulatory T cells (T reg) in terms of Foxp3 expression and suppression of CD3-stimulated or allogeneic effector cell proliferation. Transfer of congenic Thy1.1 CD4+CD25- T cells, from mice treated or not with vinblastine, into tumor-bearing or tumor-free mice and analysis of recovered donor lymphocytes indicate that conversion is the main mechanism for acquiring the expression of CD25 and Foxp3 through a process that does not require proliferation. Although conversion of CD4+CD25- T cells for generation of T regs has been described as a natural process that maintains peripheral T-reg population, this process is used by the tumor for immune escape. The prompt recovery of T regs from monoclonal antibody-mediated CD25 depletion in tumor-bearing mice suggests attempts able to inactivate rather than deplete them when treating existing tumors. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/16618776/Tumor_induced_expansion_of_regulatory_T_cells_by_conversion_of_CD4+CD25__lymphocytes_is_thymus_and_proliferation_independent_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=16618776 DB - PRIME DP - Unbound Medicine ER -