Frequencies of CD4+ T cells reactive with Plasmodium chabaudi chabaudi: distinct response kinetics for cells with Th1 and Th2 characteristics during infection.
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.
Langhorne
J
J
Max-Planck-Institut für Immunbiologie, Freiburg, FRG.
Gillard
S
S
Simon
B
B
Slade
S
S
Eichmann
K
K
D000818:Animals; D000953:Antigens, Protozoan; D015704:CD4 Antigens; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D007700:Kinetics; D008288:Malaria / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D010961:Plasmodium / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000953:Antigens, Protozoan; D015704:CD4 Antigens; D007376:Interleukin-2; D007371:Interferon-gamma