Requirements for the maintenance of Th1 immunity in vivo following DNA vaccination: a potential immunoregulatory role for CD8+ T cells.
Protective immunity against Leishmania major generated by DNA encoding the LACK (Leishmania homologue of receptor for activated C kinase) Ag has been shown to be more durable than vaccination with LACK protein plus IL-12. One mechanism to account for this may be the selective ability of DNA vaccination to induce CD8+ IFN-gamma-producing T cells. In this regard, we previously reported that depletion of CD8+ T cells in LACK DNA-vaccinated mice abrogated protection when infectious challenge was done 2 wk postvaccination. In this study, we extend these findings to study the mechanism by which CD8+ T cells induced by LACK DNA vaccination mediate both short- and long-term protective immunity against L. major. Mice vaccinated with LACK DNA and depleted of CD8+ T cells at the time of vaccination or infection were unable to control infection when challenge was done 2 or 12 wk postvaccination. Remarkably, it was noted that depletion of CD8+ T cells in LACK DNA-vaccinated mice was associated with a striking decrease in the frequency of LACK-specific CD4+ IFN-gamma-producing T cells both before and after infection. Moreover, data are presented to suggest a mechanism by which CD8+ T cells exert this regulatory role. Taken together, these data provide additional insight into how Th1 cells are generated and sustained in vivo and suggest a potentially novel immunoregulatory role for CD8+ T cells following DNA vaccination.
Gurunathan
S
S
Clinical Immunology Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Niational Institutes of Health, Bethesda, MD 20892, USA.
Stobie
L
L
Prussin
C
C
Sacks
D L
DL
Glaichenhaus
N
N
Iwasaki
A
A
Fowell
D J
DJ
Locksley
R M
RM
Chang
J T
JT
Wu
C Y
CY
Seder
R A
RA
D000818:Animals; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D016054:DNA, Protozoan / Q000008:administration & dosage / Q000276:immunology; D019674:Genes, T-Cell Receptor beta; D007106:Immune Sera / Q000008:administration & dosage; D007111:Immunity, Cellular; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D018320:Leishmania major / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000517:prevention & control; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011493:Protein Kinase C / Q000378:metabolism; D015800:Protozoan Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D053707:Receptors, Interleukin-12; D018417:Th1 Cells / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology*
D000953:Antigens, Protozoan; D016827:CD8 Antigens; D016054:DNA, Protozoan; D007106:Immune Sera; D015800:Protozoan Proteins; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D019444:Vaccines, DNA; C093139:LACK antigen, Leishmania; D018664:Interleukin-12; D007371:Interferon-gamma; D011493:Protein Kinase C