TY - JOUR
T1 - Population dynamics and gene regulation of T cells in response to chronic antigen stimulation
AU - Hsiung, Sunnie
AU - Egawa, Takeshi
N1 - Funding Information:
This work is supported by the United States National Institutes of Health grants R01AI130152, R21AI161040, R03AI139875 (T.E.), and T32CA009547 (S.H.). Acknowledgments
Publisher Copyright:
© The Author(s) 2022. Published by Oxford University Press on behalf of The Japanese Society for Immunology. All rights reserved.
PY - 2023/2/1
Y1 - 2023/2/1
N2 - T cells are activated by antigen and co-stimulatory receptor signaling and undergo robust proliferation and differentiation into effector cells with protective function. Such quantitatively and qualitatively amplified T cell responses are effective in controlling acute infection and are followed by contraction of the effector population and the formation of resting memory T cells for enhanced protection against previously experienced antigens. However, in the face of persistent antigen during chronic viral infection, in autoimmunity, or in the tumor microenvironment, T cells exhibit distinct responses relative to those in acute insult in several aspects, including reduced clonal expansion and impaired effector function associated with inhibitory receptor expression, a state known as exhaustion. Nevertheless, their responses to chronic infection and tumors are sustained through the establishment of hierarchical heterogeneity, which preserves the duration of the response by generating newly differentiated effector cells. In this review, we highlight recent findings on distinct dynamics of T cell responses under “exhausting” conditions and the roles of the transcription factors that support attenuated yet long-lasting T cell responses as well as the establishment of dysfunctional states.
AB - T cells are activated by antigen and co-stimulatory receptor signaling and undergo robust proliferation and differentiation into effector cells with protective function. Such quantitatively and qualitatively amplified T cell responses are effective in controlling acute infection and are followed by contraction of the effector population and the formation of resting memory T cells for enhanced protection against previously experienced antigens. However, in the face of persistent antigen during chronic viral infection, in autoimmunity, or in the tumor microenvironment, T cells exhibit distinct responses relative to those in acute insult in several aspects, including reduced clonal expansion and impaired effector function associated with inhibitory receptor expression, a state known as exhaustion. Nevertheless, their responses to chronic infection and tumors are sustained through the establishment of hierarchical heterogeneity, which preserves the duration of the response by generating newly differentiated effector cells. In this review, we highlight recent findings on distinct dynamics of T cell responses under “exhausting” conditions and the roles of the transcription factors that support attenuated yet long-lasting T cell responses as well as the establishment of dysfunctional states.
KW - T cell exhaustion
KW - T cell memory
KW - immune check point
KW - progenitors
UR - http://www.scopus.com/inward/record.url?scp=85147892828&partnerID=8YFLogxK
U2 - 10.1093/intimm/dxac050
DO - 10.1093/intimm/dxac050
M3 - Review article
C2 - 36334059
AN - SCOPUS:85147892828
SN - 0953-8178
VL - 35
SP - 67
EP - 77
JO - International Immunology
JF - International Immunology
IS - 2
ER -