International Immunology Advance Access originally published online on September 7, 2009
International Immunology 2009 21(11):1213-1224; doi:10.1093/intimm/dxp085
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CD4 T cell cooperation is required for the in vivo activation of CD4 T cells
1 Department of Microbiology and Immunology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Saskatchewan, Canada S7N 5E5
2 Present address: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Building 4, Room B1-12, 4 Center Drive, Bethesda, MD 20892-0425, USA
Correspondence to: P. A. Bretscher; E-mail: peter.bretscher{at}usask.ca or N. C. Peters; E-mail: NPeters{at}niaid.nih.gov
We address here the role of CD4 T cell cooperation in the activation of CD4 T cells. Administration of aggregated hen egg lysozyme (HEL) without microbial adjuvant to BALB/c mice normally generates cytokine-producing CD4 T cells specific for the HEL major peptide, HEL105–120, as well as CD4 T cells specific for HEL non-major peptides. The prior administration of HEL105–120 ablates the generation of cytokine-secreting CD4 T cells specific for HEL105–120, as well as the CD4 T cells specific for HEL non-major peptides, normally generated upon HEL challenge. Thus, the activation of HEL non-major peptide-specific CD4 T cells appears to depend upon the HEL105–120-specific CD4 T cell population. In contrast, when HEL105–120 and saline-treated mice are challenged with HEL coupled to ovalbumin (OVA), CD4 T cell responses to HEL non-major peptides and to OVA are the same, whereas treated mice still do not generate cytokine-secreting cells specific for HEL105–120. We infer that the administration of HEL105–120 does not generate regulatory cells capable of down-regulating CD4 T cell responses to HEL and OVA peptides. OVA-specific CD4 T cells restore the generation of HEL non-major peptide-specific T cells in the absence of HEL major peptide-specific T cells. We conclude that the generation of CD4 T cells producing IL-2, IFN-
and IL-4 requires CD4 T cell cooperation and that this cooperation is not mediated simply by CD40–CD40L interactions. We also conclude from these observations that there is no requirement for a microbial or danger signal for CD4 T cell activation.
Keywords: CD4 T cell activation, CD4 T cell cooperation, peripheral tolerance
Transmitting editor: A. Singer
Received 18 August 2008, accepted 6 August 2009.