CD8 + T Lymphocytes Are Not Required for Murine Resistance to Human Filarial Parasites

Abstract

Mice are resistant to the establishment of infection with the nematode parasite Brugia malayi, an etiologic agent of human lymphatic filariasis. We have recently shown that T and B lymphocyte-deficient C.B.-17 scid/scid mice are permissive for infection with this parasite, whereas coisogenic C.B.-17+/+ mice are resistant. This observation suggests that T and B lymphocytes that comprise the antigen-specific immune system orchestrate murine resistance to B. malayi. In order to define the component of the antigen-specific immune response that is responsible for this resistance, we have tested the susceptibility of beta 2M-/- mice to infection with B. malayi L3 larvae. These mice are homozygous for insertional disruption of their B2m genes, which encode beta 2-microglobulin, the small subunit of the major histocompatibility (MHC) antigens. They do not express beta 2-microglobulin and, as a consequence, fail to express the class I major histocompatibility antigens, and they do not develop the CD8+ class I MHC-restricted cytotoxic T cell subset. We find that these mice are completely resistant to B. malayi, indicating that the CD8+ T lymphocyte subset is not an obligate requirement for murine resistance to human filarial parasites.

Differentially enhanced cytokine gene expression in CD4+ and CD8+ T cells in mesenteric lymph nodes in rats infected with Nippostrongylus brasiliensis

“…Recent studies using IL-13 knockout mice indicated that IL-13 plays a critical role in expelling N. brasiliensis, and may be more important than IL-4 as an inducer of Stat6 signalling that leads to worm expulsion (McKenzie et al 1998, Urban et al 1998). These results do not contradict previous observations that the depletion of CD8 þ T cells has little effects on protection against intestinal nematode infection (Katona et al 1988, Urban et al 1991, Rajan et al 1992) because the expression of the IL-13 gene was remarkably enhanced in CD4 þ T cells after infection.…”

CD4+ T lymphocytes mediate in vivo clearance of plasmid DNA vaccine antigen expression and potentiate CD8+ T-cell immune responses

“…Because MHC class I presentation of peptide antigen to CD8 ϩ T cells requires ␤2m, the ␤2m KO mice cannot generate antigen-specific CD8 ϩ T-cell responses. 18,19 Surprisingly, we did not observe a difference in the kinetics of expression of luciferase between the ␤2m KO and wild-type mice (Figure 2A). We next depleted CD8 ϩ T cells from wild-type mice by treating them with an anti-CD8␣ antibody before immunization with plasmid DNALuc ( Figure 2B).…”

Immunology of lymphatic filariasis

“…Both nude mice (that lack T cells) and SCID or Rag‐deficient mice (that lack both T and B cells) are susceptible to infection with Brugian parasites, indicating that T cells are absolutely critical for elimination of infection. It appears, however, that either T‐cell subset – CD4 + or CD8 + T cells – can mediate resistance in nonpermissive animals because mice that lack either CD4 + T cells or CD8 + T cells are fully capable of resisting infection . In addition, protective immunity to filarial infections in mice is dependent primarily on Th2 responses in mice.…”