Effector CD8+ T lymphocytes against liver stages of Plasmodium yoelii do not require gamma interferon for antiparasite activity

Abstract

The protective immune response against liver stages of the malaria parasite critically requires CD8(+) T cells. Although the nature of the effector mechanism utilized by these cells to repress parasite development remains unclear, a critical role for gamma interferon (IFN-gamma) has been widely assumed based on circumstantial evidence. However, the requirement for CD8(+) T-cell-mediated IFN-gamma production in protective immunity to this pathogen has not been directly tested. In this report, we use an adoptive transfer strategy with circumsporozoite (CS) protein-specific transgenic T cells to examine the role of CD8(+) T-cell-derived IFN-gamma production in Plasmodium yoelii-infected mice. We show that despite a marginal reduction in the expansion of naive IFN-gamma-deficient CS-specific transgenic T cells, their antiparasite activity remains intact. Further, adoptively transferred IFN-gamma-deficient CD8(+) T cells were as efficient as their wild-type counterparts in limiting parasite growth in naive mice. Taken together, these studies demonstrate that IFN-gamma secretion by CS-specific CD8(+) T cells is not essential to protect mice against live sporozoite challenge.

FIG. 1.

(a) BALB/c mice received TCR-Tg cells obtained from WT or IFNγKO transgenic mice and were immunized with 2 × 10⁶ vaccinia virus. Eight days later, the number of tetramer⁺CD8⁺ cells was determined by FACS analysis and is plotted as a proportion of total CD8⁺ cells within splenocytes and hepatic lymphocyte populations. (b) IL-2-secreting cells within the same populations were identified by ELISPOT assay. Histograms represent means ± the standard errors of the mean (n = 4).

FIG. 2.

(a) BALB/c mice received TCR-Tg CD8⁺ T cells isolated from WT or IFNγKO mice and were immunized with 2 × 10⁶ PFU VV-CS. Eight days later, mice were challenged with 3.5 × 10⁴ P. yoelii sporozoites and parasite-specific rRNA levels in the liver determined by quantitative RT-PCR. (b) Mice received WT or IFNγKO TCR-Tg CD8⁺ T cells and were immunized as described for panel a. Eight days later, 2 × 10⁶ purified TCR-Tg CD8⁺ spleen cells were recovered and retransferred into secondary naive BALB/c hosts that were subsequently challenged with 3.5 × 10⁴ P. yoelii sporozoites. The parasite load in the liver was evaluated as for panel a. Each bar represents a single mouse. A Student t test was used to evaluate statistical significance.