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The Journal of Immunology, Vol 150, Issue 8 3602-3614, Copyright © 1993 by American Association of Immunologists

ARTICLES

Patterns of cytokine gene expression by CD4+ T cells from young and old mice

MV Hobbs, WO Weigle, DJ Noonan, BE Torbett, RJ McEvilly, RJ Koch, GJ Cardenas and DN Ernst
Scripps Research Institute, Department of Immunology, La Jolla, CA 92037.

We have analyzed the patterns of induced cytokine gene expression and cell cycle activity by CD4+ cells from mice, and have examined how these response patterns change during the aging process. CD4+ cells were isolated from spleens of young adult and old C57BL/6NNia mice and were stimulated in vitro with plate-bound anti-CD3 epsilon mAb. The cells were then assessed over time for the capacity to accumulate transcripts for IL-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IFN-gamma, TNF-alpha, and TNF-beta; to secrete IL-2, IL-3, IL-4, IL-5, IL-6, and IFN-gamma; and to progress through S phase. Before the first major cell division in culture (< 32 h), stimulated CD4+ cells of the old group contained similar peak levels of IL-2, TNF-alpha, and TNF- beta transcripts relative to young adult controls, whereas IL-3, IL-4, IL-5, and IFN-gamma transcripts accumulated to significantly higher peak levels in the old group. These findings were consistent with the patterns of cytokine secretion later in culture (24 to 72 h): the peak IL-2 levels were similar between age groups, but the old group exhibited an enhanced capacity to release IL-3, IL-4, IL-5, and IFN- gamma. In contrast, CD4+ cells of the young group were superior in the hyper-expression of the housekeeping gene, rpL32, before cell division and in the levels of S phase activity throughout 3-day cultures. Similar analyses of CD4+ cells from mice of intermediate ages showed that the alterations in cytokine profiles occurred gradually from young adulthood to old age, whereas the reductions in proliferative capacity were late life changes. Consistent with previous reports, we found that the splenic CD4+ cell group also underwent a progressive, age-dependent increase in the proportions of cells expressing high levels of membrane CD44 (a phenotype associated with memory or effector cells). Moreover, the analysis of IL-3, IL-5, and IFN-gamma production by isolated CD4+CD44lo and CD4+CD44hi cells revealed that the capacity to produce these cytokines segregated predominantly with the CD44hi subset, regardless of donor age. Taken together, our data suggest that gradual age-associated shifts in the subset composition of the splenic CD4+ cell pool underlie progressive changes in the patterns of cytokine gene expression by this cell group.


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Decreased Expression of Th2 Type Cytokine mRNA Contributes to the Lack of Allergic Bronchial Inflammation in Aged Rats
J. Immunol., July 1, 1999; 163(1): 396 - 402.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
E. G. Barrett, C. Johnston, G. Oberdorster, and J. N. Finkelstein
Silica-induced chemokine expression in alveolar type II cells is mediated by TNF-alpha -induced oxidant stress
Am J Physiol Lung Cell Mol Physiol, June 1, 1999; 276(6): L979 - L988.
[Abstract] [Full Text] [PDF]

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 JEMHome page
L. G. Guidotti, P. Borrow, A. Brown, H. McClary, R. Koch, and F. V. Chisari
Noncytopathic Clearance of Lymphocytic Choriomeningitis Virus from the Hepatocyte
J. Exp. Med., May 17, 1999; 189(10): 1555 - 1564.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
C. L. Wohlford-Lenane, D. C. Deetz, and D. A. Schwartz.
Cytokine gene expression after inhalation of corn dust
Am J Physiol Lung Cell Mol Physiol, May 1, 1999; 276(5): L736 - L743.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
L. M. Bradley, V. C. Asensio, L.-K. Schioetz, J. Harbertson, T. Krahl, G. Patstone, N. Woolf, I. L. Campbell, and N. Sarvetnick
Islet-Specific Th1, But Not Th2, Cells Secrete Multiple Chemokines and Promote Rapid Induction of Autoimmune Diabetes
J. Immunol., March 1, 1999; 162(5): 2511 - 2520.
[Abstract] [Full Text] [PDF]

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 J. Cell Sci.Home page
M. Nieman, J. Kim, K. Johnson, and M. Wheelock
Mechanism of extracellular domain-deleted dominant negative cadherins
J. Cell Sci., January 5, 1999; 112(10): 1621 - 1632.
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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
E. G. Barrett, C. Johnston, G. Oberdorster, and J. N. Finkelstein
Silica-induced chemokine expression in alveolar type II cells is mediated by TNF-alpha
Am J Physiol Lung Cell Mol Physiol, December 1, 1998; 275(6): L1110 - L1119.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
L. A. Dickinson, R. J. Gulizia, J. W. Trauger, E. E. Baird, D. E. Mosier, J. M. Gottesfeld, and P. B. Dervan
Inhibition of RNA polymerase II transcription in human cells by synthetic DNA-binding ligands
PNAS, October 27, 1998; 95(22): 12890 - 12895.
[Abstract] [Full Text] [PDF]

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 Am. J. Pathol.Home page
A. K. Stalder, M. J. Carson, A. Pagenstecher, V. C. Asensio, C. Kincaid, M. Benedict, H. C. Powell, E. Masliah, and I. L. Campbell
Late-Onset Chronic Inflammatory Encephalopathy in Immune-Competent and Severe Combined Immune-Deficient (SCID) Mice with Astrocyte-Targeted Expression of Tumor Necrosis Factor
Am. J. Pathol., September 1, 1998; 153(3): 767 - 783.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
A.-K. Yi, M. Chang, D. W. Peckham, A. M. Krieg, and R. F. Ashman
CpG Oligodeoxyribonucleotides Rescue Mature Spleen B Cells from Spontaneous Apoptosis and Promote Cell Cycle Entry
J. Immunol., June 15, 1998; 160(12): 5898 - 5906.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
A. J. Rajan, J. D. S. Klein, and C. F. Brosnan
The Effect of {gamma}{delta} T Cell Depletion on Cytokine Gene Expression in Experimental Allergic Encephalomyelitis
J. Immunol., June 15, 1998; 160(12): 5955 - 5962.
[Abstract] [Full Text] [PDF]

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 J. Virol.Home page
F. Rodriguez, L. L. An, S. Harkins, J. Zhang, M. Yokoyama, G. Widera, J. T. Fuller, C. Kincaid, I. L. Campbell, and J. L. Whitton
DNA Immunization with Minigenes: Low Frequency of Memory Cytotoxic T Lymphocytes and Inefficient Antiviral Protection Are Rectified by Ubiquitination
J. Virol., June 1, 1998; 72(6): 5174 - 5181.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
M. Falcone, A. J. Rajan, B. R. Bloom, and C. F. Brosnan
A Critical Role for IL-4 in Regulating Disease Severity in Experimental Allergic Encephalomyelitis as Demonstrated in IL-4-Deficient C57BL/6 Mice and BALB/c Mice
J. Immunol., May 15, 1998; 160(10): 4822 - 4830.
[Abstract] [Full Text] [PDF]

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 BloodHome page
R. A. Nazaruk, R. Rochford, M. V. Hobbs, and M. J. Cannon
Functional Diversity of the CD8+ T-Cell Response to Epstein-Barr Virus (EBV): Implications for the Pathogenesis of EBV-Associated Lymphoproliferative Disorders
Blood, May 15, 1998; 91(10): 3875 - 3883.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
A. N. Vallejo, A. R. Nestel, M. Schirmer, C. M. Weyand, and J. J. Goronzy
Aging-related Deficiency of CD28 Expression in CD4+ T Cells Is Associated with the Loss of Gene-specific Nuclear Factor Binding Activity
J. Biol. Chem., April 3, 1998; 273(14): 8119 - 8129.
[Abstract] [Full Text] [PDF]

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 J. Virol.Home page
V. J. Cavanaugh, L. G. Guidotti, and F. V. Chisari
Inhibition of Hepatitis B Virus Replication during Adenovirus and Cytomegalovirus Infections in Transgenic Mice
J. Virol., April 1, 1998; 72(4): 2630 - 2637.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
A.-K. Yi and A. M. Krieg
CpG DNA Rescue from Anti-IgM-Induced WEHI-231 B Lymphoma Apoptosis via Modulation of I{kappa}B{alpha} and I{kappa}B{beta} and Sustained Activation of Nuclear Factor-{kappa}B/c-Rel
J. Immunol., February 1, 1998; 160(3): 1240 - 1245.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
K. L. Knutson, Z. Hmama, P. Herrera-Velit, R. Rochford, and N. E. Reiner
Lipoarabinomannan of Mycobacterium tuberculosis Promotes Protein Tyrosine Dephosphorylation and Inhibition of Mitogen-activated Protein Kinase in Human Mononuclear Phagocytes. ROLE OF THE Src HOMOLOGY 2 CONTAINING TYROSINE PHOSPHATASE 1
J. Biol. Chem., January 2, 1998; 273(1): 645 - 652.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
T. W. Wright, C. J. Johnston, A. G. Harmsen, and J. N. Finkelstein
Analysis of Cytokine mRNA Profiles in the Lungs of Pneumocystis carinii-infected Mice
Am. J. Respir. Cell Mol. Biol., October 1, 1997; 17(4): 491 - 500.
[Abstract] [Full Text]

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 Arch DermatolHome page
C. Sunderkotter, H. Kalden, and T. A. Luger
Aging and the Skin Immune System
Arch Dermatol, October 1, 1997; 133(10): 1256 - 1262.
[Abstract] [PDF]

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 J. Biol. Chem.Home page
B. S. Finlin and D. A. Andres
Rem Is a New Member of the Rad- and Gem/Kir Ras-related GTP-binding Protein Family Repressed by Lipopolysaccharide Stimulation
J. Biol. Chem., August 29, 1997; 272(35): 21982 - 21988.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
C. J. Johnston, G. W. Mango, J. N. Finkelstein, and B. R. Stripp
Altered Pulmonary Response to Hyperoxia in Clara Cell Secretory Protein Deficient Mice
Am. J. Respir. Cell Mol. Biol., August 1, 1997; 17(2): 147 - 155.
[Abstract] [Full Text]

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 JEMHome page
C. F. Evans, M. S. Horwitz, M. V. Hobbs, and M. B.A. Oldstone
Viral Infection of Transgenic Mice Expressing a Viral Protein in Oligodendrocytes Leads to Chronic Central Nervous System Autoimmune Disease
J. Exp. Med., December 1, 1996; 184(6): 2371 - 2384.
[Abstract] [Full Text] [PDF]


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