CD4+ T cells disarm or delete cytotoxic T lymphocytes under IL-17-polarizing conditions.
Previous studies have shown that TGF-β acts cooperatively with IL-6 to elicit a high frequency of IL-17-secreting CD4(+) T cells (termed Th17) and an elevated CD8(+)IL-17(+) T cell population (termed Tc17). These CD8(+) cells fail to behave like most cytotoxic T lymphocytes that express IFN-γ and granzyme B, but they exhibit a noncytotoxic phenotype. Although a significant increase in the number of these Tc17 cells was found in tumors, their role and interaction with other cell types remain unclear. In this study, we demonstrate that the presence of CD4(+)CD25(-) T cells, but not the CD4(+)CD25(+) (regulatory T [Treg]) cell population, significantly reduced the elicitation of Tc17 cells, possibly as a result of the induction of apoptotic signals. Importantly, these signals may be derived from soluble mediators, and the addition of anti-IL-2 restored the reduction of Tc17 cells in the presence of CD4(+)CD25(-) T cells. Finally, the elicited Tc17 and Treg cells exhibited a close association in patients with head and neck cancer, indicating that the surrounding Treg cells might maintain the survival of the Tc17 cells. Taken together, these results reveal an intriguing mechanism in which Tc17 cells are controlled by a finely tuned collaboration between the different types of CD4(+) T cells in distinct tumor microenvironments.
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 350, Taiwan.
Jy-Ping
JP
Tsai
Meng-Hua
MH
Lee
Shu-Ching
SC
Hsu
Mei-Yu
MY
Chen
Shih-Jen
SJ
Liu
Joseph T
JT
Chang
Chun-Ta
CT
Liao
Ann-Joy
AJ
Cheng
Pele
P
Chong
Ching-Liang
CL
Chu
Chia-Rui
CR
Shen
Hsin-Wei
HW
Chen
D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000276:immunology; D002450:Cell Communication / Q000276:immunology*; D016764:Cell Polarity; D018920:Coculture Techniques; D005260:Female; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000276:immunology; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D060888:Real-Time Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D059016:Tumor Microenvironment / Q000276:immunology
D020381:Interleukin-17