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Infection and Immunity, April 2000, p. 2069-2076, Vol. 68, No. 4
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Interleukin-12 Neutralization Alters Lung Inflammation and Leukocyte Expression of CD80, CD86, and Major Histocompatibility Complex Class II in Mice Infected with Histoplasma capsulatum

Judith A. Cain and George S. Deepe Jr.*

Department of Medicine, Division of Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0560, and Veterans Affairs Hospital, Cincinnati, Ohio 48229

Received 11 October 1999/Returned for modification 2 December 1999/Accepted 4 January 2000

Histoplasma capsulatum induces a cell-mediated immune response in lungs and lymphoid organs of mammals. Resolution of primary infection in mice depends on interleukin-12 (IL-12), since neutralization of this monokine increases susceptibility to infection. The present study was designed to determine if blockade of IL-12 disrupts the protective immune response by altering the influx of lineage-specific cells into infected lungs and the numbers of cells expressing CD80, CD86, CD119, and major histocompatibility complex class II (MHC II) molecules. In mice given anti-IL-12, there was a 2.5-fold decrease in total numbers of T cells on days 3 to 10 of infection and a 4-fold increase in Mac-1/Gr-1+ cells on days 7 and 10 compared to infected controls. CD80+ lung cells from anti-IL-12-treated mice were 2- to 3-fold greater than those from controls on days 7 and 10, whereas the total numbers of CD86+ cells were 2- to 3-fold less and MHC II+ cells were 1.5- to 2-fold less on days 3 and 5. Cells expressing CD119 were reduced 1.5-fold on day 5. Treatment with monoclonal antibodies (MAb) to CD80, CD86, or both reduced the fungal burden slightly compared to that in rat immunoglobulin G-treated controls, whereas after IL-12 neutralization, blocking of CD80 reduced the tissue burden by 2.5-fold and this correlated with a decrease in IL-4. Regardless, mortality was not altered by treatment with MAb to CD80 or CD86. We conclude that (i) IL-12 neutralization alters the nature of the inflammatory response in lungs and the expression of CD80 and CD86 on lineage-specific cells, (ii) the immune response during infection with H. capsulatum is controlled via mechanisms independent of the CD80 and CD86 costimulatory pathways, and (iii) decreased expression of CD86 and MHC II may modulate generation of optimal protective immunity.

* Corresponding author. Mailing address: Department of Internal Medicine, Division of Infectious Diseases, University of Cincinnati Medical Center, P.O. Box 670560, Cincinnati, OH 45267-0560. Phone: (513) 558-4704. Fax: (513) 558-2089. E-mail: deepegs{at}emailuc.edu.

Infection and Immunity, April 2000, p. 2069-2076, Vol. 68, No. 4
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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