TIM-4, a receptor for phosphatidylserine, controls adaptive immunity by regulating the removal of antigen-specific T cells

Lee A. Albacker, Piia Karisola, Ya Jen Chang, Sarah E. Umetsu, Meixia Zhou, Omid Akbari, Norimoto Kobayashi, Nicole Baumgarth, Gordon J. Freeman, Dale T. Umetsu, Rosemarie H. Dekruyff

Research output: Contribution to journalArticle

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Abstract

Adaptive immunity is characterized by the expansion of an Ag-specific T cell population following Ag exposure. The precise mechanisms, however, that control the expansion and subsequent contraction in the number of Ag-specific T cells are not fully understood. We show that T cell/transmembrane, Ig, and mucin (TIM)-4, a receptor for phosphatidylserine, a marker of apoptotic cells, regulates adaptive immunity in part by mediating the removal of Ag-specific T cells during the contraction phase of the response. During Ag immunization or during infection with influenza A virus, blockade of TIM-4 on APCs increased the expansion of Ag-specific T cells, resulting in an increase in secondary immune responses. Conversely, overexpression of TIM-4 on APCs in transgenic mice reduced the number of Ag-specific T cells that remained after immunization, resulting in reduced secondary T cell responses. There was no change in the total number of cell divisions that T cells completed, no change in the per cell proliferative capacity of the remaining Ag-specific T cells, and no increase in the development of Ag-specific regulatory T cells in TIM-4 transgenic mice. Thus, TIM-4-expressing cells regulate adaptive immunity by mediating the removal of phosphatidylserine-expressing apoptotic, Ag-specific T cells, thereby controlling the number of Ag-specific T cells that remain after the clearance of Ag or infection.

Original languageEnglish (US)
Pages (from-to)6839-6849
Number of pages11
JournalJournal of Immunology
Volume185
Issue number11
DOIs
StatePublished - Dec 1 2010

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Mucin-4
Adaptive Immunity
T-Lymphocytes
Antigens
Transgenic Mice
Immunization
phosphatidylserine receptor
Phosphatidylserines
Influenza A virus
Regulatory T-Lymphocytes
Infection
Cell Division

ASJC Scopus subject areas

  • Immunology

Cite this

Albacker, L. A., Karisola, P., Chang, Y. J., Umetsu, S. E., Zhou, M., Akbari, O., ... Dekruyff, R. H. (2010). TIM-4, a receptor for phosphatidylserine, controls adaptive immunity by regulating the removal of antigen-specific T cells. Journal of Immunology, 185(11), 6839-6849. https://doi.org/10.4049/jimmunol.1001360

TIM-4, a receptor for phosphatidylserine, controls adaptive immunity by regulating the removal of antigen-specific T cells. / Albacker, Lee A.; Karisola, Piia; Chang, Ya Jen; Umetsu, Sarah E.; Zhou, Meixia; Akbari, Omid; Kobayashi, Norimoto; Baumgarth, Nicole; Freeman, Gordon J.; Umetsu, Dale T.; Dekruyff, Rosemarie H.

In: Journal of Immunology, Vol. 185, No. 11, 01.12.2010, p. 6839-6849.

Research output: Contribution to journalArticle

Albacker, LA, Karisola, P, Chang, YJ, Umetsu, SE, Zhou, M, Akbari, O, Kobayashi, N, Baumgarth, N, Freeman, GJ, Umetsu, DT & Dekruyff, RH 2010, 'TIM-4, a receptor for phosphatidylserine, controls adaptive immunity by regulating the removal of antigen-specific T cells', Journal of Immunology, vol. 185, no. 11, pp. 6839-6849. https://doi.org/10.4049/jimmunol.1001360
Albacker, Lee A. ; Karisola, Piia ; Chang, Ya Jen ; Umetsu, Sarah E. ; Zhou, Meixia ; Akbari, Omid ; Kobayashi, Norimoto ; Baumgarth, Nicole ; Freeman, Gordon J. ; Umetsu, Dale T. ; Dekruyff, Rosemarie H. / TIM-4, a receptor for phosphatidylserine, controls adaptive immunity by regulating the removal of antigen-specific T cells. In: Journal of Immunology. 2010 ; Vol. 185, No. 11. pp. 6839-6849.
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