Tissue Dynamics of CD8 Lymphocytes That Suppress Viral Replication in Cats Infected Neonatally with Feline Immunodeficiency Virus

Abstract

The purpose of this study was to determine the tissue distribution and antiviral activity of the CD8 lymphocytes that suppress the replication of feline immunodeficiency virus (FIV). Cell-associated FIV load, CD8alpha(+)beta(low) cells, and CD8 cell-mediated suppression of FIV were measured serially in the blood, thymus, and peripheral lymph nodes after neonatal inoculation. Between 6 and 10 weeks, relative numbers of CD8alpha(+)beta(low) cells increased, whereas CD8alpha(+)beta(high) cells declined in the thymus and blood of infected cats. By 12-16 weeks, the lymph nodes were enlarged because of an absolute expansion of all CD8beta subpopulations. The strength of CD8 cell-mediated FIV suppression in vitro, but not CD8alpha(+)beta(low) cell content, was correlated inversely with virus load in the thymus and blood. Thus, after neonatal FIV inoculation, CD8alpha(+)beta(low) cells first occupy the thymus and blood, where strong CD8 cell-mediated antiviral activity is linked to reduced virus load in multiple lymphoid tissues.

Characterization of a Highly Pathogenic Molecular Clone of Feline Immunodeficiency Virus Clade C

“…on May 10, 2018 by guest http://jvi.asm.org/ responses were not measured in these studies, earlier reports imply that cell-mediated responses may be responsible for the observed survival of this one offspring (5,7,13,14). The finding that the dams became infected in both experiments where they nursed infected offspring is surprising and of great interest.…”

Transmission and Immunopathogenesis of FIV in Cats as a Model for HIV

“…Noncytolytic activity can be detected as early as 1 week following infection, is seen prior to detection of cytolytic activity, and can be detected in multiple lymphoid tissues [81]. Following FIV infection, the detection of CD8+ mediated antiviral activity in tissue and blood correlates inversely with detection of virus [45]. Treatment of acutely FIV-infected cats with methylprednisone reduces the suppression of CD8+ mediated antiviral activity resulting in greater peak plasma viremia [6].…”

“…However others have shown that the presence of CD8+β lo cells alone does not correlate with a reduction in virus load [45,82]. Additional work has associated the expansion of non-cytolytic CD8+ cells with progressive down regulation of L-selectin [87] but further study is needed to fully characterize these cells.…”

FIV as a Model for HIV: An Overview

“…This elevation in the CD8 T-cell count is due to an increase in a CD8a + b low subset that is concurrent with a reduction in CD8a + b high of CD8 T-cells and involves lymphocyte populations from peripheral blood, lymph nodes, and thymus. 212,334,374,[376][377][378][379] A similar expansion of an CD8a + b low T-cell subset has also been observed in HIV-1 infection. 380,381 Furthermore, this cell population has been shown to express markers associated with lymphocyte activation and adhesion and to exhibit antiviral activity 311,376,379 comparable to a noncytolytic CD8 antiviral activity previously described for HIV-1 infection.…”

“…212,334,374,[376][377][378][379] A similar expansion of an CD8a + b low T-cell subset has also been observed in HIV-1 infection. 380,381 Furthermore, this cell population has been shown to express markers associated with lymphocyte activation and adhesion and to exhibit antiviral activity 311,376,379 comparable to a noncytolytic CD8 antiviral activity previously described for HIV-1 infection. 382,383 FIV-induced immunodeficiency is characterized by other defects that are similar to those described for HIV-1 infection and include reduced proliferative T-cell responses to mitogens, dysregulation of cytokine networks, and humoral immune response deficits.…”