Progressive loss of CD8+ T cell-mediated control of a gamma-herpesvirus in the absence of CD4+ T cells.
A unique experimental model has been developed for dissecting the integrity of CD8+ T cell-mediated immunity to a persistent gammaherpesvirus under conditions of CD4+ T cell deficiency. Respiratory challenge of major histocompatibility complex class II -/- and +/+ C57BL/6J mice with the murine gammaherpesvirus 68 (MHV-68) leads to productive infection of both lung and adrenal epithelial cells. Virus titers peak within 5-10 d, and are no longer detected after day 15. Persistent, latent infection is established concurrently in splenic and lymph node B cells, with higher numbers of MHV-68+ lymphocytes being found in all lymphoid sites analyzed from the +/+ mice concurrent with the massive, but transient splenomegaly that occurred only in this group. From day 17, however, the numbers of infected B lymphocytes were consistently higher in the -/- group, while the frequency of this population diminished progressively in the +/+ controls. Infectious MHV-68 was again detected in the respiratory tract and the adrenals of the -/- (but not the +/+) mice from day 22 after infection. The titers in these sites rose progressively, with the majority of the -/- mice dying between days 120 and 133. Even so, some CD8+ effectors were still functioning as late as 100 d after infection. Depletion of CD8+ T cells at this stage led to higher virus titers in the -/- lung, and to the development of wasting in some of the -/- mice. Elimination of the CD8+ T cells from the +/+ group (day 80) increased the numbers of MHV-68+ cells in the spleen, but did not reactivate the infection in the respiratory tract. The results are consistent with the interpretation that CD8+ T cell-mediated control of this persistent gammaherpesvirus is progressively lost in the absence of the CD4+ T cell subset. This parallels what may be happening in AIDS patients who develop Kaposi's sarcoma and various Epstein Barr virus associated disease processes.
Cardin
R D
RD
Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Brooks
J W
JW
Sarawar
S R
SR
Doherty
P C
PC
D000818:Animals; D000917:Antibody Formation; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006183:H-2 Antigens / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000254:growth & development; D007244:Infectious Mononucleosis / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D014775:Virus Activation
D006183:H-2 Antigens; D015850:Interleukin-6; D007371:Interferon-gamma