CD28 costimulation is required for the expression of T-cell-dependent cell-mediated immunity against blood-stage Plasmodium chabaudi malaria parasites.
Mice suppress the parasitemia of acute blood-stage Plasmodium chabaudi malaria by an antibody- or T-cell-dependent cell-mediated mechanism of immunity (AMI and CMI, respectively) or by both mechanisms. To determine whether CD28 costimulation is required for expression of these polar immune responses, we first compared the time courses of P. chabaudi malaria in CD28-deficient (CD28(-/-)) and CD28-intact (CD28(+/+)) mice. Acute infections in both knockout (KO) and control mice followed similar time courses, with the period of descending parasitemia being prolonged approximately 2 weeks in KO mice followed by intermittent low-grade chronic parasitemia. Infected CD28(-/-) mice produced primarily the immunoglobulin M antibody, which upon passive transfer provided partial protection against P. chabaudi challenge, suggesting that the elimination of blood-stage parasites by CD28(-/-) mice was achieved by AMI. To determine whether CD28(-/-) costimulation is required for the expression of CMI against the parasite, we compared the time courses of parasitemia in B-cell-deficient double-KO (J(H)(-/-) x CD28(-/-)) mice and control (J(H)(-/-) x CD28(+/+)) mice. Whereas control mice suppressed parasitemia to subpatent levels within approximately 2 weeks postinoculation, double-KO mice developed high levels of parasitemia of long-lasting duration. Although not required for the suppression of acute P. chabaudi parasitemia by AMI, CD28 costimulation is essential for the elimination of blood-stage parasites by CMI.
Rummel
Thomas
T
Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA.
Batchelder
Joan
J
Flaherty
Patrick
P
LaFleur
GayeLyn
G
Nanavati
Payal
P
Burns
James M
JM
Weidanz
William P
WP
D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D018106:CD28 Antigens / Q000235:genetics / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D007106:Immune Sera / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology; D007116:Immunization, Passive; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D008288:Malaria / Q000276:immunology* / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018512:Parasitemia / Q000276:immunology / Q000469:parasitology; D016788:Plasmodium chabaudi / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
D000913:Antibodies, Protozoan; D018106:CD28 Antigens; D007106:Immune Sera; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma