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Infection and Immunity, August 2004, p. 4486-4493, Vol. 72, No. 8
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.8.4486-4493.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Characterization of an I-E-Restricted, gp63-Specific, CD4-T-Cell Clone from Leishmania major-Resistant C3H Mice That Secretes Type 2 Cytokines and Exacerbates Infection with L. major

Cynthia M. Theodos,1 Robin V. Morris,2 Jeanette V. Bishop,2 Jeremy D. Jones,2 W. Robert McMaster,3 and Richard G. Titus2*

Biogen, Inc., Cambridge, Massachusetts 02142,1 Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523,2 Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada3

Received 9 February 2004/ Returned for modification 21 March 2004/ Accepted 19 April 2004

A T-cell clone (designated KLmB-3) was derived from resistant C3H mice 2 weeks after infection with Leishmania major. KLmB-3 was a CD4-T-cell clone that utilized the Vß8.1 T-cell receptor. When adoptively transferred to naive C3H mice, KLmB-3 unexpectedly exacerbated infection with L. major (it increased the cutaneous lesion size and the parasite burden within the lesion). The ability of KLmB-3 to exacerbate disease correlated with its ability to produce the type 2-associated cytokines interleukin-4 (IL-4), IL-5, IL-10, and transforming growth factor beta. Interestingly, KLmB-3 was specific for an epitope in the amino-terminal end of the L. major surface gp63 zinc metalloproteinase (leishmanolysin) that has been shown to be capable of inducing a protective immune response. Moreover, KLmB-3 was activated when this epitope was presented in the context of H-2 I-E rather than H-2 I-A.


* Corresponding author. Mailing address: Department of Microbiology, Immunology and Pathology, CVMBS, Colorado State University, 1619 Campus Delivery, Fort Collins, CO 80523-1619. Phone: (970) 491-1607. Fax: (970) 491-0603. E-mail: richard.titus{at}colostate.edu.

Editor: W. A. Petri, Jr.


Infection and Immunity, August 2004, p. 4486-4493, Vol. 72, No. 8
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.8.4486-4493.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.