| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Division of Viral Immunology, Center for AIDS Research, Kumamoto University, Kumamoto, Japan
Multicolor flow cytometric analysis for the expression of three effector molecules, i.e., perforin (Per), granzyme A (GraA), and granzyme B (GraB), in human CD8+ T cells demonstrated that they included five subpopulations, implying the following pathway for the differentiation of CD8+ T cells: Per–GraA–GraB–
Per–GraA+GraB–PerlowGraA+GraB– PerlowGraA+GraB+PerhighGraA+GraB+. The analysis of the expression of these molecules in the subsets classified by the combination of the expression of CCR7 and CD45RA or by that of CD27, CD28, and CD45RA showed that functional CD8+ T cell subsets could be partially identified by these phenotypic classifications. However, the functional subsets could be precisely identified by the classification using five cell surface markers or three cell surface markers and three cytolytic molecules. Per–GraA–GraB– and Per–/lowGraA+GraB– cells were predominantly found in CCR5–CCR7+ and CCR5high/lowCCR7– subsets, respectively, of CD8+ T cells expressing the CD27+CD28+CD45RA– phenotype, whereas PerlowGraA+GraB+ cells were found in the CCR5lowCCR7– subset of those expressing this phenotype and in a part of the CCR5–/lowCCR7– subset of those expressing the CD27–/lowCD28–CD45RA–/+ phenotype. Ex vivo EBV-specific CD8+ T cells, which were Perlow/–GraA+GraB–/+ cells, hardly or very weakly killed the target cells, indicating that these were not effector T cells. These findings suggest that the Per–GraA–GraB–, Per–/lowGraA+GraB–, and PerlowGraA+GraB+ cells were central memory, early effector memory, and late effector memory T cells, respectively. Per–/lowGraA+GraB– cells gained GraB expression after TCR stimulation, indicating that early effector memory T cells could differentiate into late effector and effector T cells. The present study showed the existence of three memory subsets and the pathway for their differentiation.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This research was supported by a Grant-in-Aid (17047033) for Scientific Research from the Ministry of Education, Science, Sports, and Culture, the government of Japan. H.T. is a Japan Society for the Promotion of Science Research Fellow.
2 Address correspondence and reprint requests to Dr. Masafumi Takiguchi, Division of Viral Immunology, Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan. E-mail address: masafumi{at}kaiju.medic.kumamoto-u.ac.jp
3 Abbreviations used in this paper: Per, perforin; GraA, granzyme A; GraB, granzyme B; HCMV, human CMV; NCS, newborn calf serum.
This article has been cited by other articles:
|
|
 |
|
  A. E. Hogg, G. C. Bowick, N. K. Herzog, M. W. Cloyd, and J. J. Endsley Induction of granulysin in CD8+ T cells by IL-21 and IL-15 is suppressed by human immunodeficiency virus-1 J. Leukoc. Biol., November 1, 2009; 86(5): 1191 - 1203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Zheng, M. Fujiwara, T. Ueno, S. Oka, and M. Takiguchi Strong Ability of Nef-Specific CD4+ Cytotoxic T Cells To Suppress Human Immunodeficiency Virus Type 1 (HIV-1) Replication in HIV-1-Infected CD4+ T Cells and Macrophages J. Virol., August 1, 2009; 83(15): 7668 - 7677. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bonehill, A. M.T. Van Nuffel, J. Corthals, S. Tuyaerts, C. Heirman, V. Francois, D. Colau, P. van der Bruggen, B. Neyns, and K. Thielemans Single-Step Antigen Loading and Activation of Dendritic Cells by mRNA Electroporation for the Purpose of Therapeutic Vaccination in Melanoma Patients Clin. Cancer Res., May 15, 2009; 15(10): 3366 - 3375. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kondo and M. Takiguchi Human memory CCR4+CD8+ T cell subset has the ability to produce multiple cytokines Int. Immunol., May 1, 2009; 21(5): 523 - 532. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Harari, F. B. Enders, C. Cellerai, P.-A. Bart, and G. Pantaleo Distinct Profiles of Cytotoxic Granules in Memory CD8 T Cells Correlate with Function, Differentiation Stage, and Antigen Exposure J. Virol., April 1, 2009; 83(7): 2862 - 2871. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. B. Walker, W. Miller, D. Haley, K. Floyd, B. Curti, and W. J. Urba Characterization of the Class I-Restricted gp100 Melanoma Peptide-stimulated Primary Immune Response in Tumor-Free Vaccine-draining Lymph Nodes and Peripheral Blood Clin. Cancer Res., April 1, 2009; 15(7): 2541 - 2551. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kondo, H. Takata, F. Matsuki, and M. Takiguchi Cutting Edge: Phenotypic Characterization and Differentiation of Human CD8+ T Cells Producing IL-17 J. Immunol., February 15, 2009; 182(4): 1794 - 1798. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. K. Chattopadhyay, M. R. Betts, D. A. Price, E. Gostick, H. Horton, M. Roederer, and S. C. De Rosa The cytolytic enzymes granyzme A, granzyme B, and perforin: expression patterns, cell distribution, and their relationship to cell maturity and bright CD57 expression J. Leukoc. Biol., January 1, 2009; 85(1): 88 - 97. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Dahl, A. Berson, J. Lora, and M. Fuentes A Novel CCR5-Specific Pharmacodynamic Assay in Whole Blood Using Phosphoflow Cytometry Highlights Different Ligand-Dependent Responses but Similar Properties of Antagonists in CD8+ and CD4+ T Lymphocytes J. Pharmacol. Exp. Ther., December 1, 2008; 327(3): 926 - 933. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Radziewicz, C. C. Ibegbu, H. Hon, M. K. Osborn, K. Obideen, M. Wehbi, G. J. Freeman, J. L. Lennox, K. A. Workowski, H. L. Hanson, et al. Impaired Hepatitis C Virus (HCV)-Specific Effector CD8+ T Cells Undergo Massive Apoptosis in the Peripheral Blood during Acute HCV Infection and in the Liver during the Chronic Phase of Infection J. Virol., October 15, 2008; 82(20): 9808 - 9822. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. DeBenedette, D. M. Calderhead, H. Ketteringham, A. H. Gamble, J. M. Horvatinovich, I. Y. Tcherepanova, C. A. Nicolette, and D. G. Healey Priming of a Novel Subset of CD28+ Rapidly Expanding High-Avidity Effector Memory CTL by Post Maturation Electroporation-CD40L Dendritic Cells Is IL-12 Dependent J. Immunol., October 15, 2008; 181(8): 5296 - 5305. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Okada, T. Kondo, F. Matsuki, H. Takata, and M. Takiguchi Phenotypic classification of human CD4+ T cell subsets and their differentiation Int. Immunol., September 1, 2008; 20(9): 1189 - 1199. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. B. Walker, D. Haley, U. Petrausch, K. Floyd, W. Miller, N. Sanjuan, G. Alvord, B. A. Fox, and W. J. Urba Phenotype and Functional Characterization of Long-term gp100-Specific Memory CD8+ T Cells in Disease-Free Melanoma Patients Before and After Boosting Immunization Clin. Cancer Res., August 15, 2008; 14(16): 5270 - 5283. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rehr, J. Cahenzli, A. Haas, D. A. Price, E. Gostick, M. Huber, U. Karrer, and A. Oxenius Emergence of Polyfunctional CD8+ T Cells after Prolonged Suppression of Human Immunodeficiency Virus Replication by Antiretroviral Therapy J. Virol., April 1, 2008; 82(7): 3391 - 3404. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Mintern, C. Guillonneau, F. R. Carbone, P. C. Doherty, and S. J. Turner Cutting Edge: Tissue-Resident Memory CTL Down-Regulate Cytolytic Molecule Expression following Virus Clearance J. Immunol., December 1, 2007; 179(11): 7220 - 7224. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Pedroza-Seres, M. Linares, S. Voorduin, R.-R. Enrique, R. Lascurain, Y. Garfias, and M. C. Jimenez-Martinez Pars planitis is associated with an increased frequency of effector-memory CD57+ T cells Br J Ophthalmol, October 1, 2007; 91(10): 1393 - 1398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Martino, R. Casetti, A. Sacchi, and F. Poccia Central Memory V{gamma}9V{delta}2 T Lymphocytes Primed and Expanded by Bacillus Calmette-Guerin-Infected Dendritic Cells Kill Mycobacterial-Infected Monocytes J. Immunol., September 1, 2007; 179(5): 3057 - 3064. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
