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Infect Immun, April 1998, p. 1384-1391, Vol. 66, No. 4
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Cytokine Involvement in Immunomodulatory Activity Affected by Candida albicans Mannan

Yanyun Wang,1,dagger Shaokang P. Li,1,Dagger Stephen A. Moser,2 Kenneth L. Bost,1 and Judith E. Domer1,*

Department of Microbiology and Immunology, Tulane University Medical School, New Orleans, Louisiana 70112-2699,1 and Department of Pathology, University of Alabama---Birmingham, Birmingham, Alabama 35294-00072

Received 3 October 1997/Returned for modification 18 November 1997/Accepted 13 January 1998

Candida albicans mannoprotein (MAN) administered intravenously to mice stimulates the production of splenic CD8+ effector cells which downregulate delayed hypersensitivity (DH) in immunized mice. Cytokine involvement in the induction and/or elicitation of downregulation was studied by (i) examining murine splenocytes qualitatively for mRNA for interleukin-2 (IL-2), IL-4, IL-10, IL-12p40, and gamma interferon (IFN-gamma ), (ii) quantitating splenocyte mRNA for IL-12p40 by quantitative-competitive reverse transcriptase-mediated PCR, and (iii) measuring serum levels of IL-12p40 and IL-12p70 by capture enzyme-linked immunosorbent assay, each performed at selected intervals over 96 h after giving MAN. Further, the effect of in vivo administration of anti-IL-4 on the induction and elicitation of MAN-specific DH in MAN-treated mice was measured. Expression of IL-12p40 mRNA in the spleen was reduced to near 0 during the first 24 h but rebounded thereafter. Transcripts for IL-10 were present throughout the 96-h period, whereas those for IL-4 and IFN-gamma were either weak or undetectable prior to 24 to 48 h. In vivo administration of anti-IL-4 partially abrogated the downregulatory effect of MAN only when given at the time of MAN administration. Serum levels of IL-12p40, but not IL-12p70, were increased by 24 h and maximal at 48 h. The antagonistic effect of IL-12p40 could contribute to the mechanism(s) for downregulation of DH. Moreover, IL-10, IL-4, and/or IFN-gamma , interacting with MAN-activated cells in the absence of biologically active IL-12, may induce the production of CD8+ downregulatory effector cells. Partial abrogation of downregulatory activity in animals treated with anti-IL-4 at the time of induction of such activity lends support to this hypothesis.

* Corresponding author. Present address: Cratis D. Williams Graduate School, Appalachian State University, Boone, NC 28608. Phone: (828) 262-2130. Fax: (828) 262-2709. E-mail: domerje{at}appstate.edu.

dagger Present address: Alton Ochsner Medical Foundation, New Orleans, LA 70121.

Dagger Present address: Sidney Kimmel Cancer Center, San Diego, CA 92121.




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