Frequencies of CD4⁺ T cells reactive with Plasmodium chabaudi chabaudi: distinct response kinetics for cells with T_h1 and T_h2 characteristics during infection

Abstract

The functional heterogeneity of the CD4+ T cell response to Plasmodium chabaudi has been evaluated. Using a limiting dilution assay system and a variety of assays to detect gamma-interferon (IFN-gamma), interleukin-2 (IL-2), IL-3, and T helper (Th) cells for malaria-specific antibody production, the precursor frequencies of P. chabaudi-reactive T cells have been calculated. The patterns of lymphokines produced by individual microcultures of the limiting dilution assay generally supported the idea of two functionally distinct CD4+ subsets: one which produces IFN-gamma and IL-2 (Th1) and one which is an effective helper cell for antibody production (Th2). However, it could not be determined whether the overlapping functions observed in some cultures represented T cells which could produce all factors or separate clones which were developing in the same wells. During the first 14 days of an erythrocytic infection of P. chabaudi the predominant T cell response was of the Th1-type. The frequency of these cells decreased after 14 days. By 3 weeks after infection the CD4+ T cell response was characterized by Th2 cells, as defined by their ability to act as helper cells in the production of malaria-specific antibody. These data support the hypothesis that early clearance of P. chabaudi may be antibody-independent but that the final clearance mechanism coincides with the appearance of helper cells and antibody.

The purine salvage enzyme hypoxanthine guanine xanthine phosphoribosyl transferase is a major target antigen for cell-mediated immunity to malaria

“…There is evidence that the natural immune response to malaria parasites does vary over time, and this is associated with reduced pathology (16)(17)(18)(19). T cells were given to BALB͞c SCID mice (deficient in both T and B cells) that were then exposed to two infectious episodes, each curtailed by antimalaria chemotherapy 2 days after challenge with 3-week interval between infections.…”

IgE elevation and IgE anti-malarial antibodies in Plasmodium falciparum malaria; association of high IgE levels with cerebral malaria

“…However, in many of these models antibodies also have a major role in clearing parasite loads during later phases when the mice are able to cure their infection. The formation of these antibodies is controlled by IL-4, produced by CD4' T cells of the Th2 variety [1][2][3]. In human Plasmodium falciparum malaria, we have shown that stimulation of CD4' T cells from immune donors with malaria antigen in vitro frequently induced either IFN-7 or lL-4 secretion, indicating the occurrence of distinct Thl-or Th2-like cells in the blood of these individuals [4].…”

In Vivo CD40-CD154 (CD40 Ligand) Interaction Induces Integrated HIV Expression by APC in an HIV-1-Transgenic Mouse Model

“…Blood stage infection with Plasmodium chabaudi chabaudi (AS) was maintained by weekly passages in naive mice as previously described (21). Experimental infections were initiated with i.p.…”

“…First, we studied the effect of stimulation with plasmodial Ag of splenocytes obtained from 4-wk P. chabaudi-infected animals, at the time when malaria-specific T cells are present in spleen (21,23). Addition of pRBC induced an ϳ3-fold increase in p24 production by splenocytes from malaria-infected HIV-Tg mice, compared with that induced by addition of cRBC (Fig.…”