Regulatory T cells prevent CD8 T cell maturation by inhibiting CD4 th cells at tumor sites

Chaput, Nathalie, Darrasse-Jeze, Guillaume, Bergot, Anne-Sophie, Cordier, Corinne, Ngo-Abdalla, Stacie, Klatzmann, David and Azogui, Orly (2007) Regulatory T cells prevent CD8 T cell maturation by inhibiting CD4 th cells at tumor sites. Journal of Immunology, 179 8: 4969-4978.

Author Chaput, Nathalie
Darrasse-Jeze, Guillaume
Bergot, Anne-Sophie
Cordier, Corinne
Ngo-Abdalla, Stacie
Klatzmann, David
Azogui, Orly
Title Regulatory T cells prevent CD8 T cell maturation by inhibiting CD4 th cells at tumor sites
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
1550-6606
Publication date 2007-10
Sub-type Article (original research)
Volume 179
Issue 8
Start page 4969
End page 4978
Total pages 10
Place of publication Bethesda, MD, United States
Publisher American Association of Immunologists
Language eng
Formatted abstract
Natural regulatory T cells (Tregs) are present in high frequencies among tumor-infiltrating lymphocytes and in draining lymph nodes, supposedly facilitating tumor development. To investigate their role in controlling local immune responses, we analyzed intratumoral T cell accumulation and function in the presence or absence of Tregs. Tumors that grew in normal BALB/c mice injected with the 4T1 tumor cell line were highly infiltrated by Tregs, CD4 and CD8 cells, all having unique characteristics. Most infiltrating Tregs expressed low levels of CD25Rs and Foxp3. They did not proliferate even in the presence of IL-2 but maintained a strong suppressor activity. CD4 T cells were profoundly anergic and CD8 T cell proliferation and cytotoxicity were severely impaired. Depletion of Tregs modified the characteristics of tumor infiltrates. Tumors were initially invaded by activated CD4+CD25- T cells, which produced IL-2 and IFN-γ. This was followed by the recruitment of highly cytotoxic CD8+ T cells at tumor sites leading to tumor rejection. The beneficial effect of Treg depletion in tumor regression was abrogated when CD4 helper cells were also depleted. These findings indicate that the massive infiltration of tumors by Tregs prevents the development of a successful helper response. The Tregs in our model prevent Th cell activation and subsequent development of efficient CD8 T cell activity required for the control of tumor growth. Copyright © 2007 by The American Association of Immunologists, Inc.
Keyword Immunological Self-Tolerance
In-Vivo
Immune Suppression
Peripheral-Blood
Responses
Cancer
Autoimmunity
Lymphocytes
Activation
Expression
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
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