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. 1994 Jun;62(6):2490–2498. doi: 10.1128/iai.62.6.2490-2498.1994

B cells are required for the switch from Th1- to Th2-regulated immune responses to Plasmodium chabaudi chabaudi infection.

A W Taylor-Robinson 1, R S Phillips 1
PMCID: PMC186536  PMID: 8188374

Abstract

The induction of T-helper cell subsets during the course of blood stage Plasmodium chabaudi chabaudi infection was compared in immunologically intact NIH mice and mice that were depleted of B cells from birth by treatment with anti-mu antibodies. For intact mice, in which the acute primary parasitemia peaked 10 days following infection, purified splenic CD4+ T cells recovered during the ascending parasitemia produced high levels in vitro of interleukin 2 (IL-2) (peak levels on day 10) and gamma interferon (IFN-gamma) (peak levels on day 7). Sera collected from these mice at around this time contained relatively high levels of P. c. chabaudi-specific immunoglobulin 2a (peak levels on day 12), and serum nitric oxide activity was significantly elevated at peak parasitemia. During the descending primary parasitemia, production of IFN-gamma and IL-2 decreased, while levels of IL-4 and IL-10 produced by splenic CD4+ T cells were significantly raised from the time at which subpatency was recorded (day 17) and persisted for at least 50 days. This was concomitant with a significant increase in levels of parasite-specific immunoglobulin G1, which peaked at around the time of recrudescence. Thus, in normal mice, sequential appearance of Th1 and Th2 responses was observed. In contrast, in B-cell-depleted mice, recovery from acute primary parasitemia was followed by a persistent patent infection which did not drop below 0.1% for at least 75 days after initiation of infection. These mice were unable to mount a significant Th2 response, manifest as an enduring inability of splenic CD4+ T cells to produce significant levels of IL-4 and IL-10. IL-2 and IFN-gamma levels remained significantly elevated throughout the 50-day observation period, and there was sustained production of nitric oxide. These data show that immune responses mediated by CD4+ T cells of the Th1 subset are capable of limiting infection beyond the initial acute phase, but that they do not eliminate parasitemia. Furthermore, as the progression from a Th1-regulated to a Th2-regulated immune response fails to occur in B-cell-depleted mice, the data suggest that B cells are required for the downregulation of Th1-mediated and/or the generation of Th2-mediated protective immunity to P. c. chabaudi.

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Selected References

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