Role of T-lymphocyte subsets in Rhodococcus equi infection

Abstract

Rhodococcus equi, a facultative intracellular gram-positive bacterium, can induce life-threatening infections in immunocompromised patients, especially those with AIDS. We have studied the mechanism of acquired immunity to this pathogen in a murine model. Protective immunity was induced by live but not killed bacteria. Adoptive transfer of resistance was obtained with spleen cells but not immune serum from mice immunized intravenously 30 days earlier with live bacteria. In normal mice, an intravenous challenge of 5 x 10(6) CFU of R. equi was cleared from the spleen, liver, and lungs within 3 weeks, whereas athymic nude mice were unable to clear the bacteria. In vivo depletion with monoclonal antibodies showed that both CD4+ and CD8+ T-cell subsets participate in the clearance of bacteria and that CD8+ T cells play the major role.

Live virulent Rhodococcus equi, rather than killed or avirulent, elicits protective immunity to R. equi infection in mice

“…Moreover, adoptive transfer of resistance to nude mice was not obtained by a monoclonal antibody against virulence-associated 15-to 17-kDa antigens. These results revealed that live ATCC 33701P 3 , a plasmid-cured derivative of virulent R. equi, could not elicit protective immunity, and are consistent with previous observations that protective immunity was induced by live virulent, but not killed organisms [20].…”

“…However, a strain from an AIDS isolate used in a vaccination experiment was not virulent R. equi because 50% of the lethal dose of the strain was s 10 V bacteria in BALB/c mice by the i.v. route, suggesting an avirulent R. equi [16,20].…”

“…Endogenously generated interferon-Q (IFN-Q) and tumor necrosis factor-K (TNF-K) play a crucial role in host defense against R. equi infection [17,18]. Adoptive transfer of an R. equi-speci¢c Th1 cell line to immunode¢cient mice e¡ected clearance of bacteria from the lung and prevented pneumonia [19], and vaccination with live R. equi conferred a degree of protection while killed vaccine was unable to do so [20]. However, a strain from an AIDS isolate used in a vaccination experiment was not virulent R. equi because 50% of the lethal dose of the strain was s 10 V bacteria in BALB/c mice by the i.v.…”

Rhodococcus equi Virulence-Associated Antigens and Specific Antibody Response in AIDS Patients Infected with R. equi

“…In AIDS patients, the impairment of T-cell-mediated immunity is clearly the critical determinant for the development of R. equi disease, which can be induced by both virulent and avirulent strains. Both CD4+ and CD8+ lymphocytes are important in the resistance against R. equi, even though CD8+ cells seem to play the major role in host defence (15). The results reported here suggest that, once infection is established, both the synthesis of the virulence-associated antigens and a defective humoral immune response may contribute to the severity of the disease.…”

Interaction of virulent and non-virulent Rhodococcus equi human isolates with phagocytes, fibroblast- and epithelial-derived cells

“…Cell-mediated immunity plays a major role in immunity to R. equi. Both CD4 + and CD8 + T cell subsets are required for acquired resistance to R. equi but CD8 + T cell subset plays the major role [6].…”