Back to Search
Start Over
IL-15 induces CD4 effector memory T cell production and tissue emigration in nonhuman primates.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 2006 Jun; Vol. 116 (6), pp. 1514-24. Date of Electronic Publication: 2006 May 11. - Publication Year :
- 2006
-
Abstract
- HIV infection selectively targets CD4+ effector memory T (T EM) cells, resulting in dramatic depletion of CD4+ T cells in mucosal effector sites in early infection. Regeneration of the T EM cell compartment is slow and incomplete, even when viral replication is controlled by antiretroviral therapy (ART). Here, we demonstrate that IL-15 dramatically increases in vivo proliferation of rhesus macaque (RM) CD4+ and CD8+ T EM cells with little effect on the naive or central memory T (T CM) cell subsets, a response pattern that is quite distinct from that of either IL-2 or IL-7. T EM cells produced in response to IL-15 did not accumulate in blood. Rather, 5-bromo-2'-deoxyuridine (BrdU) labeling studies suggest that many of these cells rapidly disperse to extralymphoid effector sites, where they manifest (slow) decay kinetics indistinguishable from that of untreated controls. In RMs with uncontrolled SIV infection and highly activated immune systems, IL-15 did not significantly increase CD4+ T EM cell proliferation, but with virologic control and concomitant reduction in immune activation by ART, IL-15 responsiveness was again observed. These data suggest that therapeutic use of IL-15 in the setting of ART might facilitate specific restoration of the CD4 + T cell compartment that is the primary target of HIV with less risk of exhausting precursor T cell compartments or generating potentially deleterious regulatory subsets.
- Subjects :
- Animals
Anti-Retroviral Agents immunology
Anti-Retroviral Agents therapeutic use
CD28 Antigens immunology
CD8-Positive T-Lymphocytes immunology
Cell Proliferation
HIV Infections immunology
Humans
Interleukin-15 therapeutic use
Interleukin-2 immunology
Interleukin-7 immunology
Lymphocyte Activation
Macaca mulatta
Male
Receptors, CCR7
Receptors, Chemokine immunology
Simian Acquired Immunodeficiency Syndrome drug therapy
Simian Acquired Immunodeficiency Syndrome immunology
Viral Load
Virus Replication
CD4-Positive T-Lymphocytes immunology
Cell Movement physiology
Immunologic Memory
Interleukin-15 immunology
T-Lymphocyte Subsets immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9738
- Volume :
- 116
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 16691294
- Full Text :
- https://doi.org/10.1172/JCI27564