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Blood, 15 June 2007, Vol. 109, No. 12, pp. 5346-5354.
Prepublished online as a Blood First Edition Paper on February 27, 2007; DOI 10.1182/blood-2006-10-051318.
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Submitted October 10, 2006
Accepted February 20, 2007
CD4 cells can be more efficient at tumor rejection than
CD8 cells
Ainhoa Perez-Diez*, Nathalie T Joncker, Kyungho Choi, William FN Chan, Colin C Anderson, Olivier Lantz, and Polly Matzinger
Ghost Lab, Laboratory of Cellular & Molecular Immunology, NIAID, NIH, Bethesda, MD, United States
Laboratoire d'Immunologie & U520 Inserm, Institute Curie, Paris, France
Laboratory of Cellular & Molecular Immunology, NIAID, NIH, Bethesda, MD, United States
Medical Microbiology & Immunology, University of Alberta, Edmonton, Canada
Dept of Surgery, University of Alberta, Edmonton, Canada
* Corresponding author; email: ainhoa{at}nih.gov.
Because of their potent killing activity, and their ability to reject transplanted organs, researchers designing anti-tumor treatments have long focused on eliciting tumor-specific CD8 Cytotoxic T Lymphocytes (CTL). The resulting treatments, however, have generally been surprisingly poor at inducing complete tumor rejection, both in experimental models and in the clinic. Although a few scattered studies suggested that CD4 T "helper" cells might also serve as anti-tumor effectors, they have generally been studied mostly for their ability to enhance the activity of CTL. In this mouse study we compared monoclonal populations of tumor specific CD4 and CD8 T cells as effectors against several different tumors and found that CD4 T cells eliminated tumors that were resistant to CD8-mediated rejection, even in cases where the tumors expressed MHC class I molecules but not MHC class II. MHC class II expression on host tissues was critical, suggesting that the CD4 T cells act indirectly. Indeed, the CD4 T cells partnered with NK cells to obtain the maximal anti-tumor effect. These findings suggest that CD4 T cells can be powerful anti-tumor effector cells that can, in some cases, outperform the current gold standard effector cell in tumor immunotherapy, the CD8 T cells.
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