Masters Theses

Author

Lee A. Coker

Date of Award

8-1991

Degree Type

Thesis

Degree Name

Master of Science

Major

Comparative and Experimental Medicine

Major Professor

Robert N. Moore

Committee Members

Barry Rouse, Albert Ichiki

Abstract

This study presents data outlining potential roles of T- cell subsets during systemic murine infection by Candia albicans. Dose responses were performed to determine a concentration of C. albicans providing a reliable model of lethal systemic infection. T-cell subset depletion was assayed by cytoflourography after 3 i.v. injections of GK1.5 MAb (anti-CD4+), 2.43 MAb (anti-CD8+), or a combination of these two MAb. HD151 MAb was used as control ascites (nonspecific rat 1gG) in the assays. Data indicated a 98% CD4+ depletion in normal mice: 84% in infected mice. There was a 97% CD8+ depletion in normal mice; 86% in infected mice. A survival assay using MAb depleted animals challenged with a lethal dose of Candida demonstrated that only mice treated with GK1.5 had significant survival and increased survival times. GK1.5 treated mice which survived the initial Candida challenge and were then allowed to replete their CD4+ population were as susceptible to subsequent Candida challenge as normal mice.

Other immune parameters were examined. Antibody titers were determined in depleted mice. Preliminary data indicated that titers for both 1gG and 1gM may not be significantly elevated in mice treated with GK1.5 MAb 7 days into the infection. Yeast tissue burden counts were performed showing there was no significant difference between the experimental groups in recovered yeast c.f.u. during the most critical time of infection. A DTH reaction assay revealed that only those mice receiving anti-CD4+ treatment failed to mount a measurable DTH reaction.

Data from this study indicates that T lymphocytes may be important in elimination of C. albicans but that an overactive response may produce harmful consequences to the murine host. The data is supportive of mortality with immunopathology directed through the CD4+ subset.

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