A recombinant Sendai virus is controlled by CD4+ effector T cells responding to a secreted human immunodeficiency virus type 1 envelope glycoprotein.
The importance of antigen-specific CD4(+) helper T cells in virus infections is well recognized, but their possible role as direct mediators of virus clearance is less well characterized. Here we describe a recombinant Sendai virus strategy for probing the effector role(s) of CD4(+) T cells. Mice were vaccinated with DNA and vaccinia virus recombinant vectors encoding a secreted human immunodeficiency virus type 1 (HIV-1) envelope protein and then challenged with a Sendai virus carrying a homologous HIV-1 envelope gene. The primed mice showed (i) prompt homing of numerous envelope-primed CD4(+) T cell populations to the virus-infected lung, (ii) substantial production of gamma interferon, and interleukin-2 (IL-2), IL-4, and IL-5 in that site, and (iii) significantly reduced pulmonary viral load. The challenge experiments were repeated with immunoglobulin(-/-) microMT mice in the presence or absence of CD8(+) and/or CD4(+) T cells. These selectively immunodeficient mice were protected by primed CD4(+) T cells in the absence of antibody or CD8(+) T cells. Together, these results highlight the role of CD4(+) T cells as direct effectors in vivo and, because this protocol gives such a potent response, identify an outstanding experimental model for further dissecting CD4(+) T-cell-mediated immunity in the lung.
Brown
Scott A
SA
Department of Immunology, Memphis, TN 38105, USA. scott.brown@stjude.org
Hurwitz
Julia L
JL
Zirkel
Amy
A
Surman
Sherri
S
Takimoto
Toru
T
Alymova
Irina
I
Coleclough
Chris
C
Portner
Allen
A
Doherty
Peter C
PC
Slobod
Karen S
KS
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008168:Lung / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D029082:Sendai virus / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014611:Vaccination; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
D016207:Cytokines; D015699:HIV Envelope Protein gp120