Published online before print August 4, 2006

This Article Full Text (Reprint (PDF)) All Versions of this Article: jlb.0603298v1 80/4/827    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shen, D. Articles by Radoja, S. Search for Related Content PubMed PubMed Citation Articles by Shen, D. Articles by Radoja, S.

© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0603298

Received for publication June 2, 2005.
Revised June 21, 2006.
Accepted for publication June 22, 2006.

Article

Activation of primary T lymphocytes results in lysosome development and polarized granule exocytosis in CD4⁺ and CD8⁺ subsets, whereas expression of lytic molecules confers cytotoxicity to CD8⁺ T cells

David Shen ^*, Jennifer Ma , Jacques Mather ^*, Stanislav Vukmanovic ^*, and Sasa Radoja ^*@

*Children’s National Medical Center, Center for Cancer and Immunology, Children’s Research Institute, Washington, District of Columbia; and The George Washington University, Departments of Pediatrics and Microbiology, Immunology and Tropical Medicine, Washington, District of Columbia

^@ To whom correspondence should be addressed. E-mail: sradoja{at}cnmc.org.

Abstract

Lytic granule exocytosis is the major cytotoxic mechanism used by CD8⁺ cytotoxic lymphocytes. CD8⁺ T cells acquire this effector function in the process characterized by lysosomal biogenesis, induction of expression of cytolytic molecules, and their selective sorting into the lysosomal vesicles. However, temporal relation of these differentiation stages during T cell activation has not been defined precisely. Also, although CD4⁺ T cells typically do not express lytic molecules as a consequence of activation and therefore, do not acquire granule exocytosis-mediated lytic function, it is not clear whether CD4⁺ T cells are able to degranulate. By using in vitro TCR stimulation of primary mouse lymphocytes, we found that polyclonally activated CD4⁺ T cells degranulate upon TCR ligation and polarize enlarged lysosomal granules in response to target cell recognition, despite the lack of granule exocytosis-mediated cytotoxicity. Upon TCR stimulation, resting CD8⁺ T cells rapidly express lytic molecules and acquire potent lytic function early in activation. Maximal cytolytic potential, however, depends on enlargement of lysosomal granules during the subsequent activation stages. Thus, polyclonal TCR stimulation of resting T cells results in development of lysosomal granules and their release upon TCR engagement in CD4⁺ and CD8⁺ T cells, but only CD8⁺ T cells acquire lytic function as a result of induction of expression of lytic molecules.

Key Words: mouse • cell activation

This article has been cited by other articles:

				T. B. Aydemir, J. P. Liuzzi, S. McClellan, and R. J. Cousins Zinc transporter ZIP8 (SLC39A8) and zinc influence IFN-{gamma} expression in activated human T cells J. Leukoc. Biol., August 1, 2009; 86(2): 337 - 348. [Abstract] [Full Text] [PDF]

				J. S. Y. Ma, N. Monu, D. T. Shen, I. Mecklenbrauker, N. Radoja, T. F. Haydar, M. Leitges, A. B. Frey, S. Vukmanovic, and S. Radoja Protein Kinase C{delta} Regulates Antigen Receptor-Induced Lytic Granule Polarization in Mouse CD8+ CTL J. Immunol., June 15, 2007; 178(12): 7814 - 7821. [Abstract] [Full Text] [PDF]