Clearance of HIV type 1 envelope recombinant sendai virus depends on CD4+ T cells and interferon-gamma but not B cells, CD8+ T cells, or perforin.
T cell-mediated viral clearance is classically attributed to the CD8(+) T cell subset, but CD4(+) T cells can sometimes assume this role. One such instance was illustrated by the immunization of C57BL/6 mice with HIV-1 envelope, followed by challenge with a recombinant Sendai virus (rSeV-env) carrying a gene for secreted HIV-1 envelope protein. Vaccinated mice that lacked both B cells (microMT) and CD8(+) T cells controlled virus, but control was lost when CD4(+) T cells were depleted. To explain this activity, we questioned whether CD4(+) T cells might utilize perforin for killing of MHC class II-positive targets. We also asked if the process might depend on IFN-gamma, which can upregulate MHC expression and enhance T cell recruitment to sites of virus challenge. To address these possibilities, we vaccinated perforin-KO mice with HIV-1 envelope and challenged them with rSeV-env. We found that perforin was not required for (1) CD4(+) T cell homing to the site of virus challenge, (2) expression of Th1 and Th2 cytokines (including IFN-gamma), or (3) virus clearance. To determine if IFN-gamma was required for protection, we repeated experiments in IFN-gamma-KO animals. In this case, significant protection was lost, although the CD4(+) T cells trafficked readily to the site of infection. In fact, local CD4(+) T cell numbers in vaccinated IFN-gamma- KO mice exceeded those in wild type animals. In both cases, cells were alphass TCR(+), NK-1.1(-), and CD44(+), typifying an activated CD4(+) T cell subset. Taken together, our results showed that HIV-1 envelope recombinant virus clearance was dependent on CD4(+) T cells and IFN-gamma, but occurred in the absence of B cells, CD8(+) T cells, or perforin.
Surman
Sherri L
SL
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Brown
Scott A
SA
Jones
Bart G
BG
Woodland
David L
DL
Hurwitz
Julia L
JL
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054353:Perforin / Q000276:immunology*; D029082:Sendai virus / Q000235:genetics; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
D054299:env Gene Products, Human Immunodeficiency Virus; D054353:Perforin; D007371:Interferon-gamma