help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on August 28, 2008, doi:10.1164/rccm.200806-858OC

Am. J. Respir. Crit. Care Med., Volume 178, Number 10, November 2008, 1083-1089

A more recent version of this article appeared on November 15, 2008
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
200806-858OCv1
178/10/1083    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Meintjes, G.
Right arrow Articles by Wilkinson, R. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Meintjes, G.
Right arrow Articles by Wilkinson, R. J.

Submitted on June 9, 2008
Accepted on August 28, 2008

Th1 and FoxP3 Positive T cells and the HIV-tuberculosis Immune Reconstitution Inflammatory Syndrome

Graeme Meintjes1, Katalin Andrea Wilkinson2, Molebogeng Xheeda Rangaka3, Keira Skolimowska4, Kerryn van Veen3, Musaed Abrahams5, Ronnett Seldon3, Dominique J Pepper1, Kevin Rebe6, Priscilla Mouton3, Gilles van Cutsem7, Mark Patrick Nicol3, Gary Maartens8, and Robert John Wilkinson9*

1 Institute of Infectious Diseases and Molecular Medicine and Department of Medicine, University of Cape Town, Cape Town, South Africa; GF Jooste Hospital, Manenberg, South Africa, 2 Institute of Infectious Diseases and Molecular Medicine and Department of Medicine, University of Cape Town, Cape Town, South Africa; National Institute for Medical Research, London, United Kingdom, 3 Institute of Infectious Diseases and Molecular Medicine and Department of Medicine, University of Cape Town, Cape Town, South Africa, 4 GF Jooste Hospital, Manenberg, South Africa; Division of Medicine, Imperial College London, London, United Kingdom, 5 Provincial administration of the Western Cape, Khayelitsha, South Africa, 6 GF Jooste Hospital, Manenberg, South Africa, 7 Medicins sans Frontieres, Khayelitsha, South Africa, 8 Institute of Infectious Diseases and Molecular Medicine and Department of Medicine, University of Cape Town, Cape Town, South Africa; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa, 9 Institute of Infectious Diseases and Molecular Medicine and Department of Medicine, University of Cape Town, Cape Town, South Africa; GF Jooste Hospital, Manenberg, South Africa; National Institute for Medical Research, London, United Kingdom

* To whom correspondence should be addressed. E-mail: r.j.wilkinson{at}imperial.ac.uk.

Background: The tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) induced by combination antiretroviral therapy (cART) has been attributed to dysregulated expansion of tuberculin PPD specific interferon (IFN)-gamma secreting CD4+ T cells. Methods: Longitudinal and cross-sectional studies of M. tuberculosis specific Interferon-gamma ELISpot responses and FACS analysis of blood cells from a total of 129 adults with HIV-1-associated tuberculosis, 98 of whom were prescribed cART. Results: In cross-sectional analysis the frequency of IFN-gamma secreting T cells recognising ESAT-6, alpha-crystallins (acr) 1 and 2 and PPD of M. tuberculosis was higher in TB-IRIS patients than in similar patients treated for both HIV-1 and tuberculosis who did not develop IRIS (non-IRIS, p≤0.03). The biggest difference was in recognition of acr molecules: peptide mapping indicated a polyclonal response. FACS analysis indicated equal proportions of CD4 and CD8 cells positive for activation markers HLA-DR and CD71 in both TB-IRIS and non-IRIS patients. The percentage CD4 cells positive for FoxP3 was low in both groups (TB-IRIS 5.3±4.5 versus 2.46±2.46 non-IRIS, p= 0.13). Eight weeks' longitudinal analysis of tuberculosis patients starting cART showed dynamic changes in antigen-specific IFN-gamma secreting T cells in both TBIRIS and non-IRIS groups: the only significant trend was an increased response to PPD in the TB-IRIS group (p=0.041). Conclusions: There is an association between Th1 cell expansions and TB-IRIS but the occurrence of similar expansions in non-IRIS brings into question whether these are causal. The defect in immune regulation responsible for TB-IRIS remains to be fully elucidated.
Key words: Tuberculosis, HIV, Immune Reconstitution Inflammatory Syndrome, T-Lymphocytes, FoxP3




This article has been cited by other articles:


Home page
 Clin. Microbiol. Rev.Home page
P. Price, D. M. Murdoch, U. Agarwal, S. R. Lewin, J. H. Elliott, and M. A. French
Immune Restoration Diseases Reflect Diverse Immunopathological Mechanisms
Clin. Microbiol. Rev., October 1, 2009; 22(4): 651 - 663.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. Bourgarit, G. Carcelain, A. Samri, C. Parizot, M. Lafaurie, S. Abgrall, V. Delcey, E. Vicaut, D. Sereni, B. Autran, et al.
Tuberculosis-Associated Immune Restoration Syndrome in HIV-1-Infected Patients Involves Tuberculin-Specific CD4 Th1 Cells and KIR-Negative {gamma}{delta} T Cells
J. Immunol., September 15, 2009; 183(6): 3915 - 3923.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
R. J. Wilkinson and C. Lange
Vitamin D and Tuberculosis: New Light on a Potent Biologic Therapy?
Am. J. Respir. Crit. Care Med., May 1, 2009; 179(9): 740 - 742.
[Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
W. W. Yew and C. C. Leung
Update in Tuberculosis 2008
Am. J. Respir. Crit. Care Med., March 1, 2009; 179(5): 337 - 343.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2008 American Thoracic Society 		  ATS 2008 State of the Art Course