Journal article
Restored immune response to an MHC-II-Restricted antigen in tumor-bearing hosts after elimination of regulatory T cells
Journal of pediatric surgery, Vol.39(6), pp.941-946
2004
DOI: 10.1016/j.jpedsurg.2004.02.049
PMID: 15185230
Abstract
Pediatric sarcomas have a poor prognosis, recur frequently, and are not effectively treated by currently available therapy. Immunotherapy is a promising treatment modality; however, to be successful, immune tolerance must be overcome. CD4
+CD25
+ T cells are immunosuppressive. The authors hypothesize that immune tolerance may be overcome by eliminating the regulatory CD4
+CD25
+ T cells, which are induced by tumor.
A murine fibrosarcoma (MF), which expresses an MHC-II-restricted tumor antigen (mL26), was injected subcutaneously. CD4
+ T cells were isolated and CD25
+ population examined. Monoclonal antibody was used to deplete CD25
+ T cells. Proliferation to mL26 was used to determine CD4
+ T cell response to tumor-associated antigen (TAA).
Depletion of CD25
+ cells prevented tumor establishment. Tumor-infiltrating CD25
+ T cells, which madeup 48% of CD4
+ T cells in tumors, suppressed proliferation in allogeneic mixed lymphocyte reactions. Draining lymph node cells from tumor-bearing (TB) mice did not proliferate in response to mL26, whereas those from naive mice responded vigorously. Depletion of CD25
+ cells before immunization restored response to mL26 in TB mice.
CD4
+CD25
+ T cells induced by MF facilitate tumor establishment and maintain immune tolerance. Depletion of CD4
+CD25
+ T cells may be an effective means for reversing tumor tolerance and enhancing cancer vaccines.
Details
- Title: Subtitle
- Restored immune response to an MHC-II-Restricted antigen in tumor-bearing hosts after elimination of regulatory T cells
- Creators
- Michael Nicholl - Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USAAndrew Lodge - Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USAIan Brown - Pritzker School of Medicine, University of Chicago, Chicago, IL, USASonia L Sugg - Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USAJoel Shilyansky - University of Iowa, Surgery
- Resource Type
- Journal article
- Publication Details
- Journal of pediatric surgery, Vol.39(6), pp.941-946
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.jpedsurg.2004.02.049
- PMID
- 15185230
- ISSN
- 0022-3468
- eISSN
- 1531-5037
- Language
- English
- Date published
- 2004
- Academic Unit
- Stead Family Department of Pediatrics; Surgery
- Record Identifier
- 9984051750502771
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