The Spleen CD4+ T Cell Response to Blood-Stage Plasmodium chabaudi Malaria Develops in Two Phases Characterized by Different Properties

Abstract

The pivotal role of spleen CD4+ T cells in the development of both malaria pathogenesis and protective immunity makes necessary a profound comprehension of the mechanisms involved in their activation and regulation during Plasmodium infection. Herein, we examined in detail the behaviour of non-conventional and conventional splenic CD4+ T cells during P. chabaudi malaria. We took advantage of the fact that a great proportion of CD4+ T cells generated in CD1d-/- mice are I-Ab-restricted (conventional cells), while their counterparts in I-Ab-/- mice are restricted by CD1d and other class IB major histocompatibility complex (MHC) molecules (non-conventional cells). We found that conventional CD4+ T cells are the main protagonists of the immune response to infection, which develops in two consecutive phases concomitant with acute and chronic parasitaemias. The early phase of the conventional CD4+ T cell response is intense and short lasting, rapidly providing large amounts of proinflammatory cytokines and helping follicular and marginal zone B cells to secrete polyclonal immunoglobulin. Both TNF-α and IFN-γ production depend mostly on conventional CD4+ T cells. IFN-γ is produced simultaneously by non-conventional and conventional CD4+ T cells. The early phase of the response finishes after a week of infection, with the elimination of a large proportion of CD4+ T cells, which then gives opportunity to the development of acquired immunity. Unexpectedly, the major contribution of CD1d-restricted CD4+ T cells occurs at the beginning of the second phase of the response, but not earlier, helping both IFN-γ and parasite-specific antibody production. We concluded that conventional CD4+ T cells have a central role from the onset of P. chabaudi malaria, acting in parallel with non-conventional CD4+ T cells as a link between innate and acquired immunity. This study contributes to the understanding of malaria immunology and opens a perspective for future studies designed to decipher the molecular mechanisms behind immune responses to Plasmodium infection.

miR-451 limits CD4+ T cell proliferative responses to infection in mice

“…In other disease models, such as transplant rejection, the presence of miR-451 may be protective by limiting T-cell responses. A number of studies have demonstrated that CD4 + T-cells are critical in blood stage malaria clearance in both humans [29] and mice [13, 30]. Our study indicates that miR-451 regulation of Myc expression in CD4 + T-cells impacts host immune responses.…”

Malaria among the Geriatric Population in Parts of South-Eastern Nigeria: Prevalence, Complications and Co-morbidity with Non-communicable Diseases

“…One of the reasons why older people are not particularly thought to be vulnerable to malaria complications is because it is believed that as one advances in age, partial immunity is developed against malaria. However, it is known that immune response to malaria comes along with products like cytokines involved in its pathology [18]. Furthermore the increased hormonal activities in these age groups may also be involved in severe malaria outcomes [19].…”

IFN‐γ mediates early B‐cell loss in experimental African trypanosomosis

“…Hence, the data presented here designate a double consequence of IFN‐γ signalling to the disappearance of FoB cells during T. b. brucei infection. Other infection models such as Plasmodium chabaudi show that IFN‐γ stimulates polyclonal B‐cell activation , suggesting an additional way in which IFN‐γ could contribute to FoB cell disappearance.…”