Protective CD4+ T-cell lines raised against Plasmodium chabaudi show characteristics of either Th1 or Th2 cells.
Splenic T-lymphocyte lines were established in vitro from Plasmodium chabaudi-infected NIH mice on days 16 and 20 of a primary infection, and from mice after two or three infections. Each line responded specifically to stimulation with a lysed soluble extract of P. chabaudi-infected erythrocytes (pRBC), and displayed a CD4+ (L3T4+) surface phenotype. Both the day 16 and 20 cell lines, when stimulated in vitro, secreted interleukin-2 (IL-2) and gamma-interferon (IFN-gamma), indicative of their belonging to the T helper 1 (Th1) CD4+ subset. In contrast, both lines derived from reinfected mice secreted interleukin-4 (IL-4) and provided helper activity in antibody production to P. chabaudi in vitro, and thereby had the characteristics of Th2 cells. All four T-cell lines provided significant protection to naïve mice infected with P. chabaudi. In immunocompromised mice, the day 16 T-cell line was as protective as in naïve mice whereas the cell line from mice infected twice required the additional transfer of mature naïve splenic B cells to provide protection comparable to that seen in the immunocompetent naïve recipients. The results establish that protective immunity to P. chabaudi may be associated with the induction of CD4+ T cells of either the Th1 or Th2 subset which confer protection against this malaria parasite by mechanisms independent of, and dependent upon, B-cell involvement, respectively.
Taylor-Robinson
A W
AW
Wellcome Laboratories for Experimental Parasitology, University of Glasgow, UK.
Phillips
R S
RS
D000704:Analysis of Variance; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D005260:Female; D016867:Immunocompromised Host; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008288:Malaria / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008815:Mice, Inbred Strains; D016788:Plasmodium chabaudi / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D013997:Time Factors
D000913:Antibodies, Protozoan; D007376:Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma