Augmentation of immunity to herpes simplex virus by in vivo administration of interleukin 2.
The immune mechanisms responsible for recovery from herpesvirus infections are multiple and include a principle role for aspects of T cell immunity. Our investigations add further support for this notion. We show that the ability of immune lymphocytes from animals infected i.p. 6 wk previously with herpes simplex virus type one (HSV-1) clear virus more effectively when interleukin 2 (IL 2) is injected into recipients of the adoptive transfers. Mice were treated on two consecutive days with cyclophosphamide and infected in the pinnae with 4 X 10(6) plaque-forming units of HSV-1. Three hours post-infection lymphocyte populations were injected i.v., and after a further 3 days the pinnae were removed, homogenized, and the content of infectious virus assayed. Purified IL 2 obtained from EL-4 cells either was given i.v. 2 hr before and 24 and 48 hr after cell injection or was given subcutaneously 2 hr before and 3, 24, and 48 hr after cell injection. The latter three injections were given i.p. and suspended in 15% gelatin. The immune lymphocyte cell populations were splenocytes and were either injected immediately after preparation of cell suspensions or after 5 days in vitro secondary stimulation with HSV-1. This latter cell population showed greater viral clearance activity, a function shown previously to be a property of Lyt-2+ cells. The clearance activity of cells was markedly enhanced in animals given IL 2 but only with a regimen that included injections in gelatin, a procedure that enhances in vivo circulation time of IL 2. The cell involved in clearance was a T cell and principally the Lyt-2+ subset. Treatment of recipient mice with anti-asialo GM-1 did not affect the clearance efficiency, indicating that NK cells were not responsible for the observed effect. Our experiments indicate that IL 2 may provide an important regulator of immune function in vivo and may warrant its investigation as a therapeutic agent to enhance antiviral immunity in certain circumstances.
Rouse
B T
BT
Miller
L S
LS
Turtinen
L
L
Moore
R N
RN
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D004306:Dose-Response Relationship, Immunologic; D006561:Herpes Simplex / Q000276:immunology / Q000628:therapy; D007111:Immunity, Cellular; D007116:Immunization, Passive; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000627:therapeutic use; D051379:Mice; D008809:Mice, Inbred C3H; D018139:Simplexvirus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000637:transplantation
D000276:Adjuvants, Immunologic; D007376:Interleukin-2