Hematological effects of radiant heat-induced whole body hyperthermia on dogs.

The effects on hematological parameters of radiant heat-induced whole body hyperthermia (WBH) at 40.5 degrees C and 41.8 degrees C were determined in 6 normal dogs. Complete blood counts determined prior to WBH, immediately post WBH plateau, and at 1, 2, 7, and 14 days posttreatment did not change significantly following WBH at 40.5 degrees C or 41.8 degrees C. Similarly, no significant changes were detected in platelet counts measured following 40.5 degrees C WBH. In contrast, platelet counts 11 days following 41.8 degrees C WBH increased significantly (P < 0.05) consistent with the hypothesis of induction of putative WBH-induced platelet stimulating factors.     

Experimental visceral leishmaniasis in the opossum

Adult wild-trapped opossums were infected with Leishmania donovani (Khartoum strain, WR 378) and evaluated as an animal model of visceral leishmaniasis. All infected opossums died within 32 days. Loss of body fat, hepatomegaly, and petechiae of skin and abdominal musculature were seen at necropsy. Microscopically, numerous amastigote-laden macrophages were seen in histologic sections of liver, spleen, and lymph nodes; fewer parasite-laden macrophages were in the bronchial-associated lymphoid tissues and renal glomeruli. Hematological findings included thrombocytopenia (terminal), neutropenia, and lymphopenia. Blood lymphocyte blastogenesis in response to concanavalin A and phytohemagglutinin was decreased markedly at day 24 post-infection (PI). Serum antibodies (1:40 dilution) to promastigotes of L. donovani were detected in five of eight infected opossums tested on days 10 and 24 PI. Total bilirubin concentrations and alanine aminotransferase and aspartate aminotransferase activities were increased after day 25 PI. Activated partial thromboplastin times and one-stage prothrombin times were prolonged before death. Concurrently, factors V, VIII, and XII activities were decreased.     

Suppression of neutrophil and lymphocyte function induced by a vaccinal strain of bovine viral diarrhea virus with and without the administration of ACTH

Effects of a modified live vaccine (MLV) strain of bovine viral diarrhea virus (BVD) on lymphocyte and neutrophil function were determined in cattle with and without increased plasma cortisol (hydrocortisone) concentrations. Cattle were given MLV-BVD vaccine IM and intranasally. Cattle given ACTH received 200 IU every 12 hours for 10 doses. The MLV-BVD virus when administered alone caused no apparent clinical signs or body temperature response. Of 4 MLV-BVD-treated calves that were also given ACTH, 2 developed increased body temperature and respiratory distress. The MLV-BVD virus caused a decrease in circulating lymphocytes and neutrophils, whereas administration of ACTH and MLV-BVD induced a neutrophilia and lymphopenia. The MLV-BVD virus and ACTH when administered separately or in combination caused a depression of lymphocyte blastogenesis in response to selected mitogens. Neutrophils were separated from the peripheral blood and their function was evaluated, using the following procedures: (i) random migration under agarose, (ii) ingestion of 125I-labeled Staphylococcus aureus, (iii) quantitative nitroblue tetrazolium reduction, (iv) iodination, and (v) antibody-dependent cell-mediated cytotoxicity (ADCC). The MLV-BVD virus produced a significant (P less than 0.05) suppression of neutrophil iodination and ADCC. Neutrophils from cattle given MLV-BVD virus and ACTH had enhanced random migration, enhanced S aureus ingestion, suppressed iodination, and suppressed ADCC activity.     

Phase I Evaluation of Doxorubicin and Whole-body Hyperthermia in Dogs with Lymphoma

Fifteen previously untreated dogs with histologically confirmed, high-grade multicentric lymphoma were entered into a phase I study to evaluate combined doxorubicin and whole-body hyperthermia (DOX/WBH). Groups of three, four, and eight dogs were treated with whole-body hyperthermia and concurrent doxorubicin at 12 mg/m2, 24 mg/m2 and 30 mg/m2, respectively, after one doxorubicin induction dose at 30 mg/m2. Plateau temperature (42 +/- 0.1 degree C) was maintained for 90 minutes using a radiant heating device. A total of five DOX/WBH treatments per dog were planned, and these were given every 21 days. Treatment-related toxicity was not seen in the 12-mg/m2 doxorubicin dose group. Tumor progression prohibited administration of more than three DOX/WBH treatments to any dog in the 12-mg/m2 group. Premature ventricular contractions developed after the fifth treatment in one of the four dogs treated with 24 mg/m2 of doxorubicin. Two dogs (25%) in the 30-mg/m2 dose group had treatment-related toxicity. One dog experienced acute serious myelosuppression 1 week after the third treatment. This dog received all planned DOX/WBH treatments. Asymptomatic cardiac toxicosis consisting of decreased ejection fraction and fractional shortening developed in the second dog. This dog received only two DOX/WBH treatments. The three dogs treated at 12 mg/m2 had partial responses of short duration (60-83 days). Four dogs treated at 24 mg/m2 had complete responses for 150, 164, 186, and 200 days. Eight dogs treated at 30 mg/m2 had complete responses with a mean and median duration of 241 and 190 days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cattle infected with bovine leukaemia virus may not only develop persistent B-cell lymphocytosis but also persistent B-cell lymphopenia

We investigated the distribution of B and T cells in the peripheral blood of haematologically inconspicuous (non-persistent lymphocytotic, PL-) cattle infected with the bovine leukaemia virus (BLV). Flow cytometric data were obtained from six PL- cattle and compared with six age-matched animals with persistent lymphocytosis (PL+) and five non-infected healthy controls (BLV-). In the PL- group, the percentage and number of surface immunoglobulin-positive (sIg+) B cells were significantly reduced. Whereas in BLV-cattle, about 40% of the peripheral blood lymphocytes (PBL) were sIg + and 24% were sIgM + B cells. In the PL- group, less than 20% of the PBL were sIg+ and sIgM+ B cells. Only 5% of the PBL co-expressed sIgM+ and CD5+ versus 16% in BLV-. This decrease was persistent over 3 years and predominantly affected: (i) B cells that did not express sIgM; (ii) sIgM + B cells co-expressing CD5 and CD11b; and (iii) equally both lambda- and K-type light chain B-cell subpopulations. In contrast, the number of all circulating lymphocytes, CD5- and CD11b- sIgM+ B cells and CD2+ T cells did not differ. In PL+ animals, about 75% of the PBL were sIgM+ CD5+ B cells. These cells were of polyclonal origin, as light chains of the lambda- and K-type were expressed in a ratio of 4:1 (57.7% of PBL lambda+, 14% kappa+) as in BLV- animals (33.6% of PBL lambda+, 8.7% kappa+). In PL+ cattle the absolute number of B-cells and, therefore, their relative percentage is significantly increased. For this reason, even in case of absolutely increased T-cell numbers, the relative percentage of T-cells could be lower than in normal controls. The cause for the observed B cell decrease in PL- cattle is unknown, but it can be assumed that cytotoxic T cells are involved in this B-cell lymphopenia.     

Changes of immunological response after experimentally ozonated autohemoadministration in calves.

Changes in subsets of peripheral blood mononuclear cells and lymphocyte blastogenesis reaction were observed after ozonated autohemoadministration (OAHA) in calves. Ten healthy calves were used in this study. After OAHA, CD8+ cells, CD14+ cells and WCl+cells increased (p<0.05). The level of lymphocyte blastogenesis stimulated by PHA decreased after OAHA. A significant increase in serum IL-6 activity was observed in OAHA calves. These results suggested that OAHA induced immunological changes in calves.     

Effect of surgery on the in vitro response of canine peripheral blood lymphocytes to phytohemagglutinin

The effects of surgery (ovario-hysterectomy) and anesthesia on phytohemagglutinin-induced lymphocyte blastogenesis were studied in vitro in 12 dogs. Four dogs had depressed lymphocyte blastogenic responses after surgery. This suppression was transient with normal blastogenic responses occurring in cells from all dogs 24 hours after surgery. Seemingly, T-lymphocyte function may be depressed, only transiently, after surgery.     

Experimental Ehrlichia canis infection in the dog does not cause immunosuppression

A carrier state develops in some Ehrlichia canis-infected dogs due to ineffective host defenses. The subsequent development of immune-mediated diseases or opportunistic infections in chronic ehrlichiosis suggests dysregulation of immunity; however, the immunobiology of this infection has not been well characterized. In this study, eight dogs were infected with E. canis, and changes in seroreactivity, serum immunoglobulin (Ig) concentrations, peripheral blood T cell subsets, lymphocyte blastogenesis (LBT), and lymphokine-activated killer (LAK) activity were evaluated over 4 months. Infection, which was documented by seroconversion, polymerase chain reaction, and blood culture, caused self-limiting fever and thrombocytopenia. Infected dogs developed an anti-E. canis antibody response but were not immune to re-infection. Serum IgM, IgG, and IgA concentrations were unaffected by E. canis. The percentage of circulating CD4(+) T cells was similar in uninfected and infected dogs at all points. Infected dogs developed a CD8(+) lymphocytosis 6 weeks after inoculation that subsequently subsided, despite organism persistence. Functional defects of cell-mediated immunity, measured as suppression of LAK activity or mitogen-driven LBT, were not observed. These results suggest that immune responses are not grossly impaired in young dogs during the first several months following experimental E. canis infection.     

Canine distemper virus-induced depletion of uninfected lymphocytes is associated with apoptosis

Canine distemper virus (CDV), a negative stranded RNA morbillivirus, causes a multisystemic disease in dogs, which is associated with a severe immune suppression. The aim of the study was to examine the influence of early CDV infection on leukocyte depletion, lymphopenia and virus-induced cell death in dogs infected with a virulent CDV strain. From 10 infected dogs, peripheral blood leukocytes were harvested periodically, phenotyped and analyzed for CDV antigen content and apoptosis using Annexin V-FITC and propidium iodide labeling. CDV infection induced a severe CD3+ T cell and CD21+ B cell depletion in all animals at 3 days post-infection (d.p.i.). For dogs with severe distemper, developing virus persistence in the lymphoid tissue and central nervous system, this lymphopenia lasted until the end of the experiment. Increased levels of lymphocyte apoptosis were found at 3 d.p.i., and monocyte apoptosis at 6 d.p.i. This was more prominent in the group of animals with severe distemper. At 3 d.p.i. no leukocyte infection was detectable indicating that the early lymphocyte depletion and apoptosis was not a direct consequence of virus infection. Taken together, our results demonstrate that CDV-induced lymphopenia is an early event and that the degree of lymphocyte depletion correlates with the severity of disease and virus persistence in the lymphoid tissue and central nervous system.     

Flow cytometric evaluation of disseminated intravascular coagulation in a canine endotoxemia model

Sepsis is associated with substantial morbidity and mortality in dogs. Alterations in hemostasis by systemic inflammation play an important role in the pathophysiology of sepsis. To evaluate the functional hemostatic changes in sepsis, we evaluated coagulation profiles and flow cytometric measurement of P-selectin (CD62P) expression on platelets, as well as platelet-leukocyte aggregation from a lipopolysaccharide (LPS)-induced endotoxemia model in dogs (n = 7). A sublethal dose of LPS [1 mg/kg body weight (BW)] induced thrombocytopenia and increased activated partial thromboplastin time (aPTT), prothrombin time (PT), and D-dimer concentrations. Flow cytometry analysis showed a significant increase in P-selectin expression on platelets between 1 and 24 h of a total 48 h of the experiment. In addition, platelet-leukocyte aggregation was significantly increased in the early stage of endotoxemia (at 1 and < 6 h for platelet-monocyte aggregation and at 3 h for platelet-neutrophil aggregation). Our results suggest that CD62P expression on platelets and platelet-leukocyte aggregation, as measured by flow cytometry, can be useful biomarkers of disseminated intravascular coagulation (DIC) in canine sepsis. These functional changes contribute to our understanding of the pathophysiology of hemostasis in endotoxemia.     

甲硝唑对鸡离体外周血淋巴细胞的作用

对咪唑类化合物甲硝唑对离体鸡外周血淋巴细胞(PBL)增殖及伴刀豆球蛋白A(ConA)诱导细胞(CIC)活性的作用并与咪唑类化合物左旋咪唑进行了比较；甲硝唑和左旋咪唑均以剂量依赖性方式促进鸡PBL的增殖；甲硝唑和左旋咪唑与ConA对促进鸡PBL增殖均呈现协同作用；甲硝唑和左旋咪唑对脂多糖(LPS)激活鸡PBL均具有明显促增殖作用；甲硝唑和左旋咪唑均可逆转磷酸组胺和肾上肾对ConA和nLPS激活鸡PBL增殖的抑制作用；高浓度左旋咪唑(100～400μg／mL)可明显逆转氢化可的松对ConA激活鸡PBL增殖的抑制作用，各种浓度甲硝唑和左旋咪唑均可明显逆转氢化可的松对LPS激活鸡PBL增殖的抑制作用；甲硝唑和左旋咪唑均可促进CD^ 4细胞增殖，抑制CE^ 8细胞增殖，使CD^ 4／CD^ 8细胞比值升高，CIC活性增强。     

Correlation of serum concentration of alpha 1-acid glycoprotein with lymphocyte blastogenesis and development of experimentally induced or naturally acquired hepatic abscesses in cattle.

Changes in serum alpha 1-acid glycoprotein (alpha 1AG) concentration in cattle with hepatic abscesses were observed, and function of alpha 1AG was evaluated, particularly its influence on cellular immune response. Test cattle (n = 4) were inoculated with Fusobacterium necrophorum, control cattle (n = 2) were inoculated with inactivated bacteria, and naturally affected cattle (n = 11) were found in a slaughterhouse. Determination of alpha 1AG was made by use of a single radial immunodiffusion method. The action on lymphocyte blastogenesis was determined by [3H]thymidine incorporation. Cultured lymphocytes from healthy cattle were treated with variable concentrations of alpha 1AG purified from serum obtained from cattle with hepatic abscesses and suppression of blastogenesis stimulated by each of 3 mitogens was measured. In cattle with experimentally induced abscesses, serum alpha 1AG concentration increased for 7 to 10 days after F necrophorum inoculation, its change being parallel to that of sialic acid. High concentration of alpha 1AG was found in naturally affected cattle and was highly correlated to sialic acid concentration. Suppression of lymphocyte blastogenesis in cattle with experimentally induced hepatic abscesses was highly correlated to serum alpha 1-AG concentration.     

Establishment of an IL-2-dependent bovine T cell line and an assay of lymphocyte response inhibition in leukemic bovine serum.

The mechanism of immunosuppression induced by leukemic bovine serum was investigated with respect to lymphokine reactions using an interleukin 2 (IL-2)-dependent bovine T cell line generated from bovine peripheral blood lymphocytes (PBLs). The suppression of concanavalin A (con A)-induced PBL blastogenesis was observed at a high rate in leukemic cattle sera. The growth of IL-2-dependent bovine T cells and IL-2 production from con A-induced bovine PBLs were also inhibited by these sera, and particularly, the latter was correlated significantly to the degree of lymphocyte blastogenesis by the mitogen. Therefore, the lesser sensitivity of lymphocytes to IL-2 and the reduced IL-2 production by activated lymphocytes seem to play a role in suppressing the lymphocyte reaction.     

Regulation of mitogen- and TCGF-induced lymphocyte blastogenesis by prostaglandins and supernatant from equine embryos and endometrium

Immunosuppressive substances which interfere with lymphocyte blastogenesis are released in vitro by embryos and endometrium from mares in early pregnancy. Immunosuppression was not evident when tissues were cultured in the presence of indomethacin (a prostaglandin-synthesis inhibitor). Various prostaglandins (PGs) were added to equine lymphocytes and lymphocyte proliferation was measured after the addition of concanavalin A (Con A) or phytohaemagglutinin A (PHA). PGE2 and PGF2 alpha inhibited Con A-induced blastogenesis down to final concentrations of 1.8 x 10(-9) M and 1.3 x 10(-6) M, respectively. Other PGs tested (6-keto-PGF1 alpha and 13,14-dihydro-15-keto-PGF2 alpha) did not affect Con A-induced blastogenesis. PHA-induced blastogenesis was inhibited by concentrations down to 1.8 x 10(-9) M PGE2, 3.3 x 10(-7) M PGF2 alpha and 2.8 x 10(-4) M 6-keto-PGF1 alpha. At all concentrations, 13,14-dihydro-15-keto-PGF2 alpha only slightly reduced PHA-induced blastogenesis. Therefore, PGE2 was the only prostaglandin tested which, at physiological concentrations, significantly inhibited incorporation of [3H] thymidine. The mechanism of PGE2-mediated suppression was studied by adding PGE2 and T cell growth factors (TCGF) to TCGF-responsive lymphocytes. PGE2 reduced the TCGF-mediated blastogenic response in a dose-dependent manner. Furthermore, culture supernatant from embryos and endometrium from 14-day pregnant mares inhibited lymphocyte blastogenesis induced by TCGF. These results show that PGE2 interferes with lymphocyte blastogenesis by TCGF-dependent mechanisms. It is suggested that the PGE2 present in the uterus of the early pregnant mare may be one of the factors involved in immunosuppression at the time of maternal recognition of pregnancy.     

Expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor on B-1a cell from persistent lymphocytosis (PL) cows and lymphoma cell induced by bovine leukemia virus

The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on B lymphocytes from persistent lymphocytosis (PL) cattle and lymphoma cells induced by bovine leukemia virus (BLV) was studied in vitro. Flow cytometric analysis showed that high levels of receptors to GM-CSF were expressed on these cell types. Proliferation of these B cells was induced in response to bovine GM-CSF. In tumor cell lines, the rate of cell proliferation was correlated with expression of GM-CSF receptors. A monoclonal antibody to GM-CSF inhibited lymphocyte proliferation and blocked the GM-CSF binding of lymphocytes. Cells expressing GM-CSF receptor were Ig positive and both CD5 and CD11 positive (B-1a cell). These results suggest that an abnormal expression of GM-CSF receptors on B lymphocytes from PL and lymphoma cells induced by BLV plays important roles in the PL and proliferation of lymphoma.     

Haematological and febrile response to Escherichia coli lipopolysaccharide in 12‐week‐old cockerels of genetically diverse layer lines fed diets with increasing L‐arginine levels

Due to its decisive function in the avian metabolic, endocrine and immune system L‐arginine (Arg) is dietary indispensable for chickens. In 12‐week‐old cockerels of two high‐ and two low‐performing purebred layer lines, the effects of increasing dietary Arg on the haematological and febrile response were studied over 48 h after single lipopolysaccharide (LPS) injection. The offered diets contained Arg equivalent to 70%, 100% and 200% of recommended supply. Pathophysiological alterations in weight gain, feed intake, body temperature and differential blood count were examined in comparison with their physiological initial values. Within the first 24 h after LPS injection, cockerels reduced feed intake and lost body weight subsequently. Thereby, low‐performing genotypes lost body weight to a lesser extent than high‐performing ones. The loss of body weight was further intensified by deficient dietary Arg. Within the following 24 h, cockerels recovered by improving feed intake and weight gain. Furthermore, LPS induced genotype‐specific fever response: both brown genotypes showed initial hypothermia followed by longer lasting moderate hyperthermia, whereas the white genotypes exhibited biphasic hyperthermia. Fever response was accompanied by significant changes in differential blood counts. Characterized by lymphopenia and heterophilia, a severe leucopenia was observed from 4 to 8 h after LPS injection and replaced by a marked leucocytosis with longer lasting monocytosis up to 48 h after LPS injection. Under given pathophysiological conditions, deficiently Arg‐supplied cockerels showed higher total leucocyte counts than adequately and excessively Arg‐supplied cockerels. However, deficient and surplus dietary Arg tended to cause higher ratios between heterophils and lymphocytes. To conclude, present results confirmed that LPS induced numerous immunological changes in 12‐week‐old cockerels and emphasized that chicken's genotype is a source of variation to be considered for immunological studies. Deficient dietary Arg intensified acute changes in differential blood counts and weight gain during LPS‐induced inflammation.     

Early events in the immunopathogenesis of feline retrovirus infections.

Feline leukemia virus and feline immunodeficiency virus (FIV) are lymphotropic retroviruses that cause a wide range of diseases in domestic cats. Although it is known that both viruses are capable of infecting T lymphocytes and that infected cats are lymphopenic, it was not known how infection with either virus might alter specific lymphocyte subpopulations. Using a panel of monoclonal antibodies to feline lymphocyte subpopulations, we examined, by use of flow cytometric analysis, lymphocyte changes in cats naturally infected with FeLV or FIV and explored the early stages in the immunopathogenesis of experimentally induced infection with these viruses. Both groups of naturally infected cats had T-cell lymphopenia. In the FIV-infected cats, the T-cell decrease was principally attributable to loss of CD4+ cells, whereas CD8+ and B-cell numbers remained normal. This led to inversion of the CD4+ to CD8+ ratio in these cats. In contrast, the T-cell lymphopenia in FeLV-infected cats resulted from decrease in CD4+ and CD8+ cells, which led to a CD4+ to CD8+ ratio within normal limits. Experimentally induced infection with these 2 viruses supported these findings. Infection with FIV induced early (10 weeks after infection), chronic inversion of the CD4+ to CD8+ ratio. In contrast, infection with FeLV did not alter CD4+ to CD8+ ratio in the first 20 weeks after infection.     

Interaction of acute feline herpesvirus-1 and chronic feline immunodeficiency virus infections in experimentally infected specific pathogen free cats.

Cats with or without chronic feline immunodeficiency virus (FIV) infection were exposed to feline herpesvirus, type 1 (FHV-1). FIV infected cats became sicker than non-FIV infected cats and required more supportive treatment. However, there were no differences in the length of their illness or in the levels and duration of FHV-1 shedding. FHV-1 infection caused a transient neutrophilia at Day 7 with a rapid return to preinfection levels. The neutrophilia coincided with a transient lymphopenia that was accompanied by a decline in both CD4+ and CD8+ T-lymphocytes. A brief decrease in the CD4+/CD8+ T-lymphocyte ratio occurred at Day 14 in both FIV infected and non-infected cats. This decrease was mainly the result of an absolute and transient increase in CD8+ T-lymphocytes. CD4+ and CD8+ T-lymphocyte numbers and CD4+/CD8+ T-lymphocyte ratios returned to baseline within 4-8 weeks in both FIV infected and non-infected cats. FIV infected cats produced less FHV-1 neutralizing antibodies during the first 3 weeks of infection than non-FIV infected animals. The IgM FHV-1 antibody response was depressed in FIV infected cats whereas the IgG antibody response was unaffected. FHV-1 infection evoked a comparable transient loss of lymphocyte blastogenic responses to concanavalin A and pokeweed mitogen in both FIV infected and non-infected cats. However, response to pokeweed mitogen took longer to return to normal in FIV infected animals. Lymphocytes from FIV infected cats had a greater and more sustained proliferative response to FHV-1 antigen than non-FIV infected cats. The ongoing IgG antibody response to FIV was not affected by FHV-1 infection.     

Effect of serum on lymphocyte blastogenesis I. Basic characteristics of action by diseased dog serum

The immunoregulatory effect of serum on phytomitogen-induced lymphocyte blastogenesis was studied in 4 sera from diseased dogs and 1 serum from a clinically healthy dog. The results indicated that: (1) Each of the diseased animals responded to the given infection with a specific pattern of blastogenesis inhibition. (2) The blastogenesis suppression $\text{in vitro}$ was proportional to the content of the suppressive serum in the medium. (3) A simultaneous presence of the mitogen and the suppressing “serum's lymphocyte immunoregulatory factors” (SLIF) was necessary for inducing blastogenesis suppression. (4) The suppressive sera most probably acted directly on the cells. (5) The final effect of the sera on lymphocyte blastogenesis was a result of an orchestrated action of blastogenesis-supporting, augmenting, and suppressing SLIF cooperating with the mitogen. (6) The suppressive pattern varied with the individual peripheral blood lymphocytes populations used in the test. (7) The blastogenesis-suppressing SLIF was heat-stable, noncytotoxic, and was not or only partially removable by absorption with peripheral blood lymphocytes. (8) The testing of SLIF activities required the use of various animal lymphocytes and a relatively complex setup of mitogens and control serum combinations for correct interpretations.     

Alterations in lymphocyte subpopulations in peripheral blood of sheep persistently infected with border disease virus.

Fourteen sheep persistently infected with border disease virus were investigated to examine the effects of persistent viraemia on lymphocyte subpopulations in peripheral blood and their responses to the mitogen phytohaemagglutinin (PHA) in vitro. Persistently infected sheep had significantly more CD8+ (cytotoxic-suppressor) T-lymphocytes than uninfected sheep of the same age (P less than 0.001). The total number of CD4+ (helper) T-lymphocytes were not significantly different but there were more T-lymphocytes (CD5+) which were CD4- and CD8- in normal sheep than persistently infected sheep (P less than 0.001). Peripheral lymphocytes obtained from persistently infected sheep showed significantly reduced blastogenesis induced by PHA than those obtained from normal sheep (P less than 0.001).