Frequencies of CD4+ T cells reactive with Plasmodium chabaudi chabaudi: distinct response kinetics for cells with Th1 and Th2 characteristics during infection

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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 γ-interferon (IFN-γ), interleukln-2 (IL-2), IL-3, and T helper (Th) cells for malaria-specific antibody production, the precursor frequencies of P. chabaudl-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-γ and IL-2 (Th1) and one which Is an effective helper cell for antibody production (Th2) However, it could not be determined whether the overiapping 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-tupe. 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.

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