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Journal of Virology, October 2006, p. 10151-10161, Vol. 80, No. 20
0022-538X/06/$08.00+0     doi:10.1128/JVI.02670-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

CD127+CCR5+CD38+++ CD4+ Th1 Effector Cells Are an Early Component of the Primary Immune Response to Vaccinia Virus and Precede Development of Interleukin-2+ Memory CD4+ T Cells

John J. Zaunders,1*,{dagger} Wayne B. Dyer,2,3,{dagger} Mee Ling Munier,1,4 Susanna Ip,1,4 Jie Liu,2,3 Elisabeth Amyes,5 William Rawlinson,6 Robert De Rose,7 Stephen J. Kent,7 John S. Sullivan,2,3 David A. Cooper,1,4 and Anthony D. Kelleher1,4

Centre for Immunology, St. Vincent's Hospital and University of NSW, Sydney, NSW, Australia,1 Viral Immunology Laboratory, Tissue Typing Department, Australian Red Cross Blood Service, Sydney, NSW 2000, Australia,2 Transfusion Medicine and Immunogenetics Research Unit, Faculty of Medicine, University of Sydney, NSW 2006, Australia,3 National Centre in HIV Epidemiology and Clinical Research, University of NSW, Sydney, NSW, Australia,4 John Curtin School of Medical Research, ANU, Canberra, ACT, Australia,5 Virology Division, Microbiology Department, Prince of Wales Hospital, Sydney, NSW, Australia,6 Department of Microbiology and Immunology, University of Melbourne, Parkville, VIC, Australia7

Received 20 December 2005/ Accepted 9 June 2006

The stages of development of human antigen-specific CD4+ T cells responding to viral infection and their differentiation into long-term memory cells are not well understood. The inoculation of healthy adults with vaccinia virus presents an opportunity to study these events intensively. Between days 11 and 14 postinoculation, there was a peak of proliferating CCR5+CD38+++ CD4+ effector cells which contained the cytotoxic granule marker T-cell intracellular antigen 1 and included gamma interferon (IFN-{gamma})-producing vaccinia virus-specific CD4+ T cells. The majority of these initial vaccinia virus-specific CD4+ T cells were CD127+ and produced interleukin-2 (IL-2) but not CTLA-4 in response to restimulation in vitro. Between days 14 and 21, there was a switch from IFN-{gamma} and IL-2 coexpression to IL-2 production only, coinciding with a resting phenotype and an increased in vitro proliferation response. The early CCR5+CD38+++ vaccinia virus-specific CD4+ T cells were similar to our previous observations of human immunodeficiency virus (HIV)-specific CD4+ T cells in primary HIV type 1 (HIV-1) infection, but the vaccinia virus-specific cells expressed much more CD127 and IL-2 than we previously found in their HIV-specific counterparts. The current study provides important information on the differentiation of IL-2+ vaccinia virus-specific memory cells, allowing further study of antiviral effector CD4+ T cells in healthy adults and their dysfunction in HIV-1 infection.

* Corresponding author. Mailing address: Centre for Immunology, St. Vincent's Hospital, Victoria St., Darlinghurst, NSW 2010, Australia. Phone: 61-2-8382-3700. Fax: 61-2-8382-2391. E-mail: j.zaunders{at}cfi.unsw.edu.au.

{dagger} J.J.Z and W.B.D. contributed equally to this paper.

Journal of Virology, October 2006, p. 10151-10161, Vol. 80, No. 20
0022-538X/06/$08.00+0     doi:10.1128/JVI.02670-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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