The Journal of Experimental Medicine
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Published online 13 March 2000.
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© The Rockefeller University Press, 0022-1007/2000/3/937/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 6, March 20, 2000 937-948

Original Article

Self-Recognition of CD1 by {gamma}/{delta} T Cells: Implications for Innate Immunity

Franca M. Spadaa, Ethan P. Granta, Peter J. Petersb, Masahiko Sugitaa, Augustín Meliána, David S. Lesliea, Hoi K. Leec, Elly van Donselaarb, Dennis A. Hansond, Alan M. Krenskye, Otto Majdicf, Steven A. Porcellia, Craig T. Moritac, and Michael B. Brennera
a Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital at Harvard Medical School, Boston, Massachusetts 02115
b The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
c Division of Rheumatology, Department of Internal Medicine and Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa 52242
d Virginia Mason Research Center, Seattle, Washington 98101
e Division of Immunology and Transplantation Biology, Department of Pediatrics, Stanford University, Stanford, California 94305
f Institute of Immunology, University of Vienna, A-1090 Vienna, Austria

Correspondence to: Michael B. Brenner, Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, 1 Jimmy Fund Way, Boston, MA 02115. Tel:617-525-1000 Fax:617-525-1010 E-mail:mbrenner{at}rics.bwh.harvard.edu.

Released online: 13 March 2000

The specificity of immunoglobulins and {alpha}/ß T cell receptors (TCRs) provides a framework for the molecular basis of antigen recognition. Yet, evolution has preserved a separate lineage of {gamma}/{delta} antigen receptors that share characteristics of both immunoglobulins and {alpha}/ß TCRs but whose antigens remain poorly understood. We now show that T cells of the major tissue {gamma}/{delta} T cell subset recognize nonpolymorphic CD1c molecules. These T cells proliferated in response to CD1+ presenter cells, lysed CD1c+ targets, and released T helper type 1 (Th1) cytokines. The CD1c-reactive {gamma}/{delta} T cells were cytotoxic and used both perforin- and Fas-mediated cytotoxicity. Moreover, they produced granulysin, an important antimicrobial protein. Recognition of CD1c was TCR mediated, as recognition was transferred by transfection of the {gamma}/{delta} TCR. Importantly, all CD1c-reactive {gamma}/{delta} T cells express V{delta}1 TCRs, the TCR expressed by most tissue {gamma}/{delta} T cells. Recognition by this tissue pool of {gamma}/{delta} T cells provides the human immune system with the capacity to respond rapidly to nonpolymorphic molecules on professional antigen presenting cells (APCs) in the absence of foreign antigens that may activate or eliminate the APCs. The presence of bactericidal granulysin suggests these cells may directly mediate host defense even before foreign antigen-specific T cells have differentiated.

Key Words: T lymphocytes, T cell antigen receptors {gamma}/{delta}, CD1, cytolysis, granulysin


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