| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Uniformed Services University of the Health Sciences, Bethesda, MD 20814;
Department of Pathology and Lab Medicine, Emory University, Atlanta, GA 30322;
Drexel University College of Medicine, Philadelphia, PA 19129;
National Eye Institute, National Institutes of Health, Bethesda, MD 20892;
¶ AIDS and Cancer Virus Program, SAIC-Frederick, Inc., National Cancer Institute, Frederick, MD 21702; and
|| Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892
Acute SIV infection is characterized by explosive infection of memory CD4 T cells in peripheral and mucosal tissues. Interestingly, relatively few memory CD4 T cells are infected until as late as days 7–8 after challenge. However, by day 10 postinfection, most of the memory CD4 T cells are infected and carry viral DNA. The rapidity with which infection expands within 2–3 days to encompass virtually the entire memory CD4 T cell compartment suggests significant alterations in the susceptibility of memory CD4 T cells to infection during this period. The mechanism(s) underlying this increased permissiveness to infection is not known. In this study, we show that IL-15 secretion significantly correlates with the up-regulated expression of CD4 on memory CD4 T cells that is associated with increased permissiveness to SIV infection. Activation and proliferation of memory CD8, but not memory CD4 T cells, preceded the amplification of viral infection. Although memory CD4 T cells did not express normal activation markers, they displayed a significant up-regulation in the density of CD4 but not CCR5 expression between days 7 and 10 postinfection that correlated with increased plasma IL-15 levels and infection in these cells. Culture of purified CD4 T cells with IL-15 and/or SIV was associated with a significant increase in the expression of CD4 and infection of these sorted cells. Our results demonstrate that IL-15 contributes to the increased susceptibility of memory CD4 T cells to SIV during the early phase of acute SIV infection.
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 The described project was supported by Grant K22 AI07812 from the National Institutes of Allergy and Infectious Diseases and Grant R21 DE018339 from the National Institute of Dental and Craniofacial Research awarded to J.J.M. and in part from R01 AI062437 from the National Institute of Allergy and Infectious Diseases awarded to P.D.K. Studies were supported in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract NO1-CO-124000.
2 The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institute of Dental and Craniofacial Research or National Cancer Institute or the National Institutes of Health.
3 M.D.E. and M.K. contributed equally to this work.
4 Address correspondence and reprint requests to Dr. Joseph Mattapallil, Department of Microbiology and Immunology, Room B4068, Uniformed Services University, Bethesda, MD 20814. E-mail address: jmattapallil{at}usuhs.mil
5 Abbreviations used in this paper: p.i., postinfection; qPCR, quantitative PCR.
6 The online version of this article contains supplemental material.
This article has been cited by other articles:
|
|
 |
|
  Y. M. Mueller, D. H. Do, J. D. Boyer, M. Kader, J. J. Mattapallil, M. G. Lewis, D. B. Weiner, and P. D. Katsikis CD8+ Cell Depletion of SHIV89.6P-Infected Macaques Induces CD4+ T Cell Proliferation that Contributes to Increased Viral Loads J. Immunol., October 15, 2009; 183(8): 5006 - 5012. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
