Testosterone-induced abrogation of self-healing of Plasmodium chabaudi malaria in B10 mice: mediation by spleen cells

Abstract

This study investigates the suppressive effect of testosterone (Te) on the self-healing of Plasmodium chabaudi malaria in female mice of the strain C57BL/10, and, in particular, the possible role of spleen cells in mediating this Te effect. Our data show the following. (i) About 80% of B10 mice infected with 106 P. chabaudi-infected erythrocytes are capable of self-healing the infections. This capability is progressively impaired and finally abrogated after pretreating the B10 mice with Te for 3 weeks. (ii) The spleen is Te responsive. This becomes evident in a reduction of total spleen cells from 1.05 x 108 to 0.54 x 108 on average after Te treatment for 3 weeks. Moreover, Te treatment causes an increase in the relative proportion of CD8+ cells by about 4% and a decrease of Ig+ cells by about 4.5%, as revealed by flow cytometry. (iii) Spleen cells mediate the suppressive Te effect as revealed by adoptive transfer experiments. The percentage of self-healing mice dramatically decreases to about 8% when they receive, just prior to infection, nucleated spleen cells isolated from mice treated with Te for 3 weeks. This suppressive effect can be transferred by T cells in particular but also by non-T cells, though to a lesser extent. (iv) The adoptively transferred cells mediate their suppressive effect on self-healing only if the recipient mice receive Te during infection. Our data suggest that spleen cells become functionally changed by the Te treatment for 3 weeks. Particularly T cells, but also non-T cells, gain P. chabaudi-specific suppressive activities, and the cells require a Te-induced factor(s) to mediate these activities.

Estradiol binding to cell surface raises cytosolic free calcium in T cells

“…Female mice of the inbred strain C57BL/10 were obtained from our animal facilities. Spleens were aseptically removed and total nucleated spleen cells were isolated as detailed previously [21]. T cells were then prepared using the nylon‐wool procedure [22].…”

Functional testosterone receptors in plasma membranes of T cells

“…Spleens were aseptically removed from mice. Total nucleated spleen cells were isolated as detailed previously (9). T cells were then prepared using the nylon-wool procedure (17).…”

“…In some experiments, the reactions with the anti-AR antibodies were performed in the presence of 10-fold blocking peptides AR (N-20)P and AR (C-19)P, respectively (Santa Cruz Biotechnology, Heidelberg, Germany). Labeling with monoclonal antibody to mouse CD8 conjugated with phycoerythrin (CD8-PE, 1:500; Boehringer, Mannheim, Germany) and anti-mouse CD4-PE (1:200; Becton Dickinson, Heidelberg, Germany) was performed as described previously (9). Cells were analyzed in a FACScan (Becton Dickinson) with a sample size of 10,000 cells gated on the basis of forward and side scatter.…”

“…Cells were analyzed in a FACScan (Becton Dickinson) with a sample size of 10,000 cells gated on the basis of forward and side scatter. The data were stored and processed using the FACScan software as described previously (9).…”

“…In the experimental malaria Plasmodium chabaudi, for example, the suppressive effect of testosterone manifests itself as a host conversion from resistance to susceptibility: normally self-healing infections result in a fatal outcome (7,8). Concomitantly, testosterone induces a change in T cells from a resistance-promoting phenotype to a susceptibility-mediating phenotype, thus enabling the T cells to mediate the suppressive effect of testosterone (9). Other circumstantial evidence also suggests direct testosterone effects on T cells (10,11).…”