Restored immune response to an MHC-II-Restricted antigen in tumor-bearing hosts after elimination of regulatory T cells.

Abstract:

BACKGROUND/PURPOSE: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. METHODS: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). RESULTS:Depletion of CD25+ cells prevented tumor establishment. Tumor-infiltrating CD25+ T cells, which made up 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. CONCLUSIONS: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.

journal_name

J Pediatr Surg

authors

Nicholl M,Lodge A,Brown I,Sugg SL,Shilyansky J

doi

10.1016/j.jpedsurg.2004.02.049

subject

Has Abstract

pub_date

2004-06-01 00:00:00

pages

941-6; discussion 941-6

issue

6

eissn

0022-3468

issn

1531-5037

pii

S002234680400137X

journal_volume

39

pub_type

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