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Infection and Immunity, February 2000, p. 456-462, Vol. 68, No. 2
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Requirement for CD4+ T Lymphocytes in Host Resistance against Cryptococcus neoformans in the Central Nervous System of Immunized Mice

Kent L. Buchanan1,* and Hester A. Doyle2,dagger

Department of Microbiology and Immunology, Tulane University Medical Center, New Orleans, Louisiana 70112,1 and Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 731902

Received 4 August 1999/Returned for modification 30 August 1999/Accepted 26 October 1999

The importance of cell-mediated immunity (CMI) and CD4+ T lymphocytes in host resistance against Cryptococcus neoformans is well documented and is exemplified by the high susceptibility to progressive infection with this pathogen of AIDS patients with reduced CD4+ T-cell numbers. Although much has been learned about the role of CMI in the clearance of C. neoformans from the lungs and other internal organs, less is known about the protective mechanisms in the brain, the organ most frequently involved with a fatal outcome of cryptococcosis. We hypothesized that host resistance mechanisms against C. neoformans in the central nervous system (CNS) were similar to those outside the CNS (i.e., gamma interferon [IFN-gamma ], CD4+ T cells, and others). To test this hypothesis, we used a murine model of cryptococcal meningitis whereby cryptococci are introduced directly into the CNS. In experiments where mice were immunized to mount an anticryptococcal CMI response, our results indicate that immunization induced protective mechanisms that could be detected in the CNS by inhibition of the growth of viable yeast cells. Flow cytometric analyses of leukocytes in brain and spinal cord homogenates revealed that T lymphocytes, macrophages, and neutrophils accumulated in C. neoformans-infected brains of immune mice. In vivo depletion of CD4+ T cells, but not CD8+ T cells, resulted in significantly reduced leukocyte accumulation in the brains of immune mice. Furthermore, depletion of CD4+ T cells or neutralization of IFN-gamma exacerbated CNS infection in immune mice, suggesting a critical role for CMI mechanisms in acquired protection in the CNS.

* Corresponding author. Mailing address: Department of Microbiology and Immunology SL38, Tulane University Medical Center, 1430 Tulane Ave., New Orleans, LA 70112. Phone: (504) 588-5090. Fax: (504) 588-5144. E-mail: kbuchan{at}mailhost.tcs.tulane.edu.

dagger Present address: Yale University School of Medicine, Section of Rheumatology, Department of Internal Medicine, New Haven, CT 06520.

Infection and Immunity, February 2000, p. 456-462, Vol. 68, No. 2
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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