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Infection and Immunity, August 1999, p. 3786-3792, Vol. 67, No. 8
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

CTLA-4 Blockade Enhances the Immune Response Induced by Mycobacterial Infection but Does Not Lead to Increased Protection

Joanna Kirman,1 Kathy McCoy,1,dagger Sarah Hook,1 Melanie Prout,1 Brett Delahunt,2 Ian Orme,3 Anthony Frank,3 and Graham Le Gros1,*

Malaghan Institute for Medical Research1 and Department of Pathology,2 Wellington School of Medicine, Wellington South, New Zealand, and Department of Microbiology, Colorado State University, Fort Collins, Colorado 805233

Received 23 July 1998/Returned for modification 7 October 1998/Accepted 5 May 1999

The murine immune response to a pulmonary mycobacterial infection is slow to develop, allowing bacterial numbers to increase in the lung for several weeks after infection. We sought to enhance the protective immune response induced during Mycobacterium bovis BCG infection by administering an antibody that blocks the interaction of CTLA-4 with its ligands, CD80 and CD86. We found that injection of anti-CTLA-4 monoclonal antibody (MAb) greatly enhanced and accelerated the immune response, as measured by increased cellularity of the draining mediastinal lymph nodes, and enhanced antigen-inducible proliferation and gamma interferon production by mediastinal lymphocytes in vitro. However, despite the apparently enhanced immune response in the mediastinal lymph node following treatment with anti-CTLA-4 MAb, there was no improvement in clearance of mycobacteria in the lungs, liver, or spleen. Examination of the primary site of infection, the lung, revealed that CTLA-4 blockade had no effect on the number or function of lymphocytes infiltrating the infected lung tissue. Taken together, these data suggest that in vivo CTLA-4 blockade enhances mycobacterial-infection-induced lymphocyte expansion and effector cell cytokine production in the draining lymph node but does not alter the number or function of lymphocytes at the primary site of infection and therefore does not lead to enhanced clearance of the infection.

* Corresponding author. Mailing address: Malaghan Institute of Medical Research, P.O. Box 7060, Wellington South, New Zealand. Phone: 64-4-389-5096. Fax: 64-4-389-5095. E-mail: mimrglg{at}wnmeds.ac.nz.

dagger Present address: Institute of Experimental Immunology, University Hospital Zürich, 8091 Zürich, Switzerland.

Infection and Immunity, August 1999, p. 3786-3792, Vol. 67, No. 8
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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