Feline Immunodeficiency Virus Depletes Naïve (CD45RA+) CD4+ Lymphocytes from the Blood and Lymph Nodes of Domestic Cats during Acute Pediatric Infection.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3896-3896
Author(s):  
Calvin M. Johnson ◽  
Ayalew Mergia ◽  
Janelle Novak ◽  
Nazareth Gengozian
Keyword(s):  
T Lymphocytes ◽  
Lymph Nodes ◽  
Feline Immunodeficiency Virus ◽  
Pediatric Hiv ◽  
Lymphoid Tissues ◽  
Domestic Cats ◽  
Color Flow ◽  
Cd8 Cells ◽  
Immunodeficiency Virus ◽  
Cd4 Lymphocytes

Abstract Feline immunodeficiency virus (FIV) is an immunosuppressive lentivirus of domestic cats that serves as an animal model for the pathogenesis of CD4+ lymphopenia and thymus dysfunction in HIV infected humans. During most cases of adult and pediatric HIV infection, naïve CD4+ T lymphocytes recognized by the expression of the RA isoform of the leukocyte common antigen (CD45RA) are infected at a lower level than memory CD4+ T− lymphocytes; however, children with rapidly progressive disease due to thymic insufficiency harbor high levels of HIV within the CD45RA+ subpopulation. In FIV infected cats, the fate of naïve CD4 lymphocytes is unknown due to the lack of specific markers. Recently, a mAb (755) was reported to recognize the feline homologue to CD45RA, allowing the enumeration of naïve CD4 and CD8 lymphocytes in cats. The purpose of this study was to characterize the fate of CD4+CD45RA+ blood cells eight weeks after FIV infection. One-day-old kittens (n=6) were infected with virions either from a wild type clone (JSY3) or mutant ORF-A clone at equivalent reverse transcriptase units and compared to historical control data. Eight weeks after inoculation, the percentages of CD4+ and CD8+ cells belonging to the CD45RA+ subpopulation were measured by two-color flow cytometry. Both FIV inocula were associated with a reduction in total CD4+ lymphocytes from a median of 13% in controls to 8% in infected cats (P=0.004), contributing to a reduction in the CD4:CD8 ratio from 2.45 in controls to 0.76 in infected cats (P=0.007). The decline in CD4+ lymphocytes was attributable to a disproportionate loss of CD4+CD45RA+ cells: 69% of CD4+ cells were CD45RA+ in controls, as compared to 7% in FIV infected cats (P=0.004). In contrast, naïve CD8+ lymphocytes did not change significantly with FIV infection (67% of CD8+ cells were CD45RA+ in FIV infected cats as compared to 80% in controls). The distribution of CD45RA+ cells in the lymph nodes of FIV infected cats mirrored those in the blood. Together, these data suggest that acute FIV infection results in a rapid depletion of naïve CD4 lymphocytes throughout the blood and secondary lymphoid tissues, while proportions of naïve CD8 lymphocytes remain unchanged. CD4+CD45RA+ cells may be depleted during pediatric FIV infection through lytic infection or a transition to a memory phenotype lacking CD45RA.

scholarly journals Early Pathogenesis of Transmucosal Feline Immunodeficiency Virus Infection

2002 ◽  
Vol 76 (12) ◽  
pp. 6311-6322 ◽  
Author(s):  
Leslie A. Obert ◽  
Edward A. Hoover
Keyword(s):  
Lymph Nodes ◽  
Feline Immunodeficiency Virus ◽  
Mononuclear Cells ◽  
Target Cells ◽  
Lymphoid Tissues ◽  
Vaginal Mucosa ◽  
Feline Immunodeficiency Virus Infection ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Dna Pcr

ABSTRACT To identify the early target cells and tissues in transmucosal feline immunodeficiency virus (FIV) infection, cats were exposed to a clade C FIV isolate via the oral-nasal or vaginal mucosa and multiple tissues were examined by virus isolation coculture (VI), DNA PCR, catalyzed tyramide signal-amplified in situ hybridization (TSA-ISH), and immunohistochemistry between days 1 and 12 postinoculation (p.i.). FIV RNA was detected in tonsil and oral or vaginal mucosa as early as 1 day p.i. by TSA-ISH and in retropharyngeal, tracheobronchial, or external iliac lymph nodes and sometimes in spleen or blood mononuclear cells by day 2, indicating that regional and distant spread of virus-infected cells occurred rapidly after mucosal exposure. By day 8, viral RNA, DNA, and culturable virus were uniformly detected in regional and distant tissues, connoting systemic infection. TSA-ISH proved more sensitive than DNA PCR in detecting early FIV-infected cells. In mucosal tissues, the earliest demonstrable FIV-bearing cells were either within or subjacent to the mucosal epithelium or were in germinal centers of regional lymph nodes. The FIV+ cells were of either of two morphological types, large stellate or small round. Those FIV RNA+ cells which could be colabeled for a phenotype marker, were labeled for either dendritic-cell-associated protein p55 or T-lymphocyte receptor antigen CD3. These studies indicate that FIV crosses mucous membranes within hours after exposure and rapidly traffics via dendritic and T cells to systemic lymphoid tissues, a pathway similar to that thought to occur in the initial phase of infection by the human and simian immunodeficiency viruses.

scholarly journals Cytokine Response in Multiple Lymphoid Tissues during the Primary Phase of Feline Immunodeficiency Virus Infection

1998 ◽  
Vol 72 (12) ◽  
pp. 9436-9440 ◽  
Author(s):  
Gregg A. Dean ◽  
Niels C. Pedersen
Keyword(s):  
Lymph Nodes ◽  
Feline Immunodeficiency Virus ◽  
Lymphoid Tissues ◽  
Mesenteric Lymph Nodes ◽  
Cytokine Mrna ◽  
Cervical Lymph Nodes ◽  
Mesenteric Lymph ◽  
Immunodeficiency Virus ◽  
Ifn Γ

ABSTRACT Type 1 and 2 cytokine mRNA responses were measured at various time periods and in various lymphoid compartments during the acute stage (first 4 months) of feline immunodeficiency virus (FIV) infection in laboratory cats. Cytokine responses were correlated with virus replication. Virus was detected in plasma and tissue from day 14 postinfection (p.i.) onward, peaked at 56 to 70 days, and declined greatly by 70 days. Virus replication was highest in the thymus, followed by spleen, mesenteric lymph nodes, and cervical lymph nodes. Baseline cytokine levels were highest in the mesenteric lymph nodes and lowest in the cervical lymph nodes. Cytokine upregulation after FIV infection was most dramatic in the cervical lymph nodes, with the greatest increase in interleukin-10 (IL-10) and gamma interferon (IFN-γ). Cytokine transcription in the mesenteric lymph node increased above baseline by day 14 p.i. for IFN-γ, IL-12p40, IL-4, and IL-10, while elevations in the spleen were mainly for IFN-γ, IL-12p40 and IL-10. An increase in IFN-γ, IL-10, and IL-12p40 occurred in the thymus at day 56 p.i., concomitant with the onset of thymitis. In general, type 2 cytokines (IL-4 and IL-10) were increased greater than 1 log over baseline, while the elevations in type 1 cytokines were less than 1 log. In the tissues tested, CD4+ cells were the primary source of IL-2, IL-4, and IL-10. Both CD4+ and CD8+ cells produced IFN-γ, while no cytokine mRNA was detected in B cells. These results demonstrate the presence of a heterogeneous cytokine response in lymphoid tissues during the primary stage of FIV infection. The nature and intensity of the response differed from one compartment to the other and, in the case of the thymus, also with inflammatory changes. Although limited in scope, the present study confirms the usefulness of the FIV infection model in studying early cytokine events that lead to the secondary subclinical carrier state typical of most lentivirus infections.

scholarly journals Quantification of Feline immunodeficiency virus (FIVpco) in peripheral blood mononuclear cells, lymph nodes and plasma of naturally infected cougars

2006 ◽  
Vol 87 (4) ◽  
pp. 967-975 ◽  
Author(s):  
David J. Blake ◽  
Jon Graham ◽  
Mary Poss
Keyword(s):  
Virus Replication ◽  
Peripheral Blood Mononuclear Cells ◽  
Feline Immunodeficiency Virus ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Domestic Cats ◽  
Peripheral Blood Mononuclear ◽  
Viral Loads ◽  
Immunodeficiency Virus ◽  
Blood Mononuclear Cells

Infection of domestic cats with Feline immunodeficiency virus (FIV) results in a fatal immunodeficiency disease, similar to Human immunodeficiency virus 1 (HIV-1) in humans. Elevated plasma viral loads in domestic cats are correlated to decreased survival time and disease progression. However, FIV is also maintained as an apathogenic infection in other members of the family Felidae including cougars, Puma concolor (FIVpco). It is not known whether the lack of disease in cougars is a result of diminished virus replication. A real-time PCR assay was developed to quantify both FIVpco proviral and plasma viral loads in naturally infected cougars. Proviral loads quantified from peripheral blood mononuclear cells (PBMC) ranged from 2·90×101 to 6·72×104 copies per 106 cells. Plasma viral loads ranged from 2·30×103 to 2·81×106 RNA copies ml−1. These data indicate that FIVpco viral loads are comparable to viral loads observed in endemic and epidemic lentivirus infections. Thus, the lack of disease in cougars is not due to low levels of virus replication. Moreover, significant differences observed among cougar PBMC proviral loads correlated to viral lineage and cougar age (P=0·014), which suggests that separate life strategies exist within FIVpco lineages. This is the first study to demonstrate that an interaction of lentivirus lineage and host age significantly effect proviral loads.

scholarly journals Characterization of Morphologic Changes and Lymphocyte Subset Distribution in Lymph Nodes from Cats with Naturally Acquired Feline Immunodeficiency Virus Infection

1992 ◽  
Vol 29 (5) ◽  
pp. 391-399 ◽  
Author(s):  
B. A. Rideout ◽  
L. J. Lowernstine ◽  
C. A. Hutson ◽  
P. F. Moore ◽  
N. C. Pedersen
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Feline Immunodeficiency Virus ◽  
Clinical Stage ◽  
Relative Proportion ◽  
Prognostic Significance ◽  
Clinical Signs ◽  
Methyl Green ◽  
Feline Immunodeficiency Virus Infection ◽  
Immunodeficiency Virus

Lymph nodes were collected at biopsy or necropsy from 18 cats with naturally acquired symptomatic feline immunodeficiency virus (FIV) infection and from 18 seronegative cats. Thirty-five of the cats were domestic shorthairs and one was a Persian cross. The cats ranged from 7 months to 16 years of age and were mainly obtained from California veterinary practitioners, a California cattery, and a Veterinary Teaching Hospital. Based on clinical signs present at tissue collection, ten FIV-infected cats fell into the acquired immunodeficiency syndrome (AIDS)-related complex (ARC) clinical stage and eight in the terminal (AIDS) stage of FIV disease. All cats were FeLV negative by antigen ELISA. Histologic sections of lymph nodes from each cat were examined blindly and were categorized as hyperplastic, involuting, mixed hyperplastic and involuting, depleted, or normal based upon subjective evaluation of follicles and paracortex. The relative abundance of plasma cells was evaluated in methyl green pyronin (MGP) and hematoxylin and eosin-stained sections. Similar numbers of FIV-seropositive and -seronegative cats fell into each lymph node category. The only difference evident between FIV-infected cats and control cats was in the degree of plasmacytosis present; moderate to marked plasmacytosis was present in 13/18 FIV-infected cats but in only 3/18 control cats. Immunohistochemical staining of frozen lymph node sections from six FIV-infected cats and 12 control cats for CD4, CD8, Factor VIII-related antigen, and a B cell/follicular dendritic cell-specific (CD21-like) antigen revealed only a slight increase in the relative proportion of paracortical CD8+ lymphocytes versus CD4+ lymphocytes in lymph nodes from FIV-infected cats. These findings suggest that lymph node changes previously considered to be specific or highly suggestive of lentivirus-induced immunodeficiency disease are actually not specific but occur in FIV-seronegative cats as well. Despite this lack of specificity, lymph node changes seen in FIV-infected cats may have prognostic significance. All cats in the ARC stage had hyperplastic or mixed hyperplastic and involuting nodes, whereas those in the AIDS stage had either involuting or depleted nodes, which suggests that the clinical stage of disease correlates with the category of lymph node change.

scholarly journals Comparative Analysis of Cytotoxic T Lymphocytes in Lymph Nodes and Peripheral Blood of Simian Immunodeficiency Virus-Infected Rhesus Monkeys

1999 ◽  
Vol 73 (2) ◽  
pp. 1573-1579 ◽  
Author(s):  
Marcelo J. Kuroda ◽  
Jörn E. Schmitz ◽  
William A. Charini ◽  
Christine E. Nickerson ◽  
Carol I. Lord ◽  
...  
Keyword(s):  
Lymph Node ◽  
T Lymphocytes ◽  
Lymph Nodes ◽  
Peripheral Blood ◽  
Rhesus Monkeys ◽  
Tetramer Binding ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Ctl Activity

ABSTRACT Most studies of human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocytes (CTL) have been confined to the evaluation of these effector cells in the peripheral blood. What has not been clear is the extent to which CTL activity in the blood actually reflects this effector cell function in the lymph nodes, the major sites of HIV-1 replication. To determine the concordance between CTL activity in lymph nodes and peripheral blood lymphocytes (PBL), CTL specific for simian immunodeficiency virus of macaques (SIVmac) have been characterized in lymph nodes of infected, genetically selected rhesus monkeys by using both Gag peptide-specific functional CTL assays and tetrameric peptide-major histocompatibility complex (MHC) class I molecule complex staining techniques. In studies of six chronically SIVmac-infected rhesus monkeys, Gag epitope-specific functional lytic activity and specific tetrameric peptide-MHC class I staining were readily demonstrated in lymph node T lymphocytes. Although the numbers of tetramer-binding cells in some animals differed from those documented in their PBL, the numbers of tetramer-binding cells from these two different compartments were not statistically different. Phenotypic characterization of the tetramer-binding CD8+lymph node T lymphocytes of the infected monkeys demonstrated a high level of expression of the activation-associated adhesion molecules CD11a and CD49d, the Fas molecule CD95, and MHC class II-DR. These studies documented a low expression of the naive T-cell marker CD45RA and the adhesion molecule CD62L. This phenotypic profile of the tetramer-binding lymph node CD8+ T cells was similar to that of tetramer-binding CD8+ T cells from PBL. These observations suggest that characterization of AIDS virus-specific CTL activity by sampling of cells in the peripheral blood should provide a reasonable estimation of CTL in an individual’s secondary lymphoid tissue.

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