Thymic humoral factor, THF-gamma 2, enhances immunotherapy of murine cytomegalovirus (MCMV) infection by both CD4+ and CD8+ immune T cells.
Infection of mice with murine cytomegalovirus (CMV) presents a model for the study of the role of the immune system in the pathogenesis of human CMV. The contribution of the different spleen cell subsets in conferring curative immunocytotherapy to fatally MCMV-infected immunosuppressed mice was assessed using adoptive immunotherapy. It was found that the efficacy of passively transferred immune spleen cells is dose dependent and that the therapeutic effect can be enhanced considerably by treating donor mice with thymic humoral factor (THF-gamma 2). Polymerase chain reaction (PCR) of the donor spleen population was negative, indicating that no MCMV-DNA was transferred with the immune cells. Analysis of the donor mice after THF-gamma 2 treatment showed increased levels of CMV-neutralizing antibodies, while enhancement of natural killer (NK) activity was transient and lasted only during the early phase of the infection. FACS analysis demonstrated that treatment with THF-gamma 2 restored the size of both cell subsets CD4+ and CD8+ that were decreased following MCMV infection. It is shown that both CD4+ and CD8+ T-cell subsets participate in controlling the development of the fatal disease in MCMV-infected immunosuppressed recipients. It is suggested that the enhancement of the immunocompetence of both populations of spleen cells from treated donors is mediated in part by the restoration of Interleukin-2 (IL-2) production by THF-gamma 2.
Rager-Zisman
B
B
Department of Microbiology and Immunology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel.
Segev
Y
Y
Blagerman
S
S
Palmon
A
A
Tel-Or
S
S
Pecht
M
M
Trainin
N
N
Burstein
Y
Y
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000737:chemistry / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000628:therapy*; D003602:Cytotoxicity, Immunologic; D004279:DNA, Viral / Q000032:analysis; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D016219:Immunotherapy, Adoptive; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013951:Thymus Hormones / Q000627:therapeutic use*
D000914:Antibodies, Viral; D004279:DNA, Viral; D009842:Oligopeptides; D013951:Thymus Hormones; C064563:thymic humoral factor gamma 2