The role of antigen and IL-12 in sustaining Th1 memory cells in vivo: IL-12 is required to maintain memory/effector Th1 cells sufficient to mediate protection to an infectious parasite challenge.
IL-12 plays a central role in both the induction and magnitude of a primary Th1 response. A critical question in designing vaccines for diseases requiring Th1 immunity such as Mycobacterium tuberculosis and Leishmania major is the requirements to sustain memory/effector Th1 cells in vivo. This report examines the role of IL-12 and antigen in sustaining Th1 responses sufficient for protective immunity to L. major after vaccination with LACK protein (LP) plus rIL-12 and LACK DNA. It shows that, after initial vaccination with LP plus rIL-12, supplemental boosting with either LP or rIL-12 is necessary but not sufficient to fully sustain long-term Th1 immunity. Moreover, endogenous IL-12 is also shown to be required for the induction, maintenance, and effector phase of the Th1 response after LACK DNA vaccination. Finally, IL-12 is required to sustain Th1 cells and control parasite growth in susceptible and resistant strains of mice during primary and secondary infection. Taken together, these data show that IL-12 is essential to sustain a sufficient number of memory/effector Th1 cells generated in vivo to mediate long-term protection to an intracellular pathogen.
Stobie
L
L
Clinical Immunology Section, Laboratory of Clinical Investigation, Howard Hughes Medical Institute, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Gurunathan
S
S
Prussin
C
C
Sacks
D L
DL
Glaichenhaus
N
N
Wu
C Y
CY
Seder
R A
RA
D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology; D005260:Female; D007113:Immunity, Innate / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D016052:Protozoan Vaccines / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D013997:Time Factors; D014611:Vaccination; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
D000953:Antigens, Protozoan; D015704:CD4 Antigens; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D019444:Vaccines, DNA; C093139:LACK antigen, Leishmania; D018664:Interleukin-12