Control of acute cutaneous herpes simplex virus infection: T cell-mediated viral clearance is dependent upon interferon-gamma (IFN-gamma).
It is well established that T lymphocytes play a critical role in the control and clearance of herpes simplex virus (HSV) infections. However, the role of the CD4+ and CD8+ T cell subsets in the recovery process has not been clearly elucidated. Cutaneous HSV infection of the footpad tissue of C57BL/6 (B6) mice provides a model to determine the relative contribution of each T cell subset during the important early phase of the response to infection. In this study, we observed that the elimination of mature peripheral T lymphocytes by depletion in vivo with a combination of Cd4- and CD8-specific monoclonal antibodies prevented recovery from acute infection in this model. However, mice depleted of either the CD4+ or CD8+ subpopulation alone recovered completely, with only a slight delay in the total clearance of infectious virus. Adoptive transfer studies revealed that lymph node cells from donor mice selectively depleted of either CD4+ or CD8+ T cell subset in vivo, or from normal donors selectively depleted in vitro, were able to mediate recovery. As CD4-depleted mice fail to generate a CD8+ T cell-mediated cytolytic T lymphocyte (CTL) response, this suggested that the control of cutaneous HSV infections may be mediated by a cytokine-dependent mechanism common to both the CD4- and CD8+ T cell subpopulations. It was subsequently found that the neutralization of IFN-gamma in vivo diminished the ability of mice to clear infectious HSV from the skin, and treatment with anti-IFN-gamma in vivo ablated the ability of transferred T cells to mediate recovery. These studies suggested that IFN-gamma-mediated mechanisms play a critical role in the control of and recovery from acute cutaneous HSV infection.
Smith
P M
PM
Department of Microbiology and Immunology, Louisiana State University Medical Center, School of Medicine in Shreveport 71130.
Wolcott
R M
RM
Chervenak
R
R
Jennings
S R
SR
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D015704:CD4 Antigens; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens; D002461:Cell Line, Transformed; D006561:Herpes Simplex / Q000276:immunology* / Q000382:microbiology; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D018139:Simplexvirus; D012867:Skin / Q000382:microbiology / Q000528:radiation effects; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014709:Vero Cells; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens; D007371:Interferon-gamma