In the present study the therapeutic efficacy and the side effects of two antiretroviral compounds used in human acquired immunodeficiency syndrome (AIDS) research, 3'-azido-2',3'-dideoxythymidine (AZT, zidovudine, Retrovir) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA), were investigated in the treatment of cats naturally infected with feline immunodeficiency virus (FIV) and cats naturally infected with feline leukemia virus (FeLV). AZT was administered subcutaneously at a dose of 5 mg kg-1 body weight every 12 h and PMEA was administered subcutaneously at a dose of 2.5 mg kg-1 body weight every 12 h during a 3 week hospitalization. The therapeutic efficacy of both compounds was investigated. There was a stronger potency of PMEA than of AZT on the regression of stomatitis in FIV and in FeLV infected cats. In addition, in FIV infection PMEA had a stronger effect on the improvement of the general clinical status. Both antiretroviral compounds were potent agents to improve the immunologic status of FIV infected cats by raising the CD4/CD8 ratio. In FeLV infection PMEA and AZT appeared to reduce antigenemia. The hematological side effects caused by PMEA were severe and stronger than those of AZT. Therefore the advantage of PMEA in clinical and immunologic improvement was diminished by the hematologic disorders, which do not allow long term treatment with this drug in the dose used.

Biotin labeling of red cells was studied using different approaches to see if biotinylation is a useful label for determination of erythrocyte survival. Mouse red cells were labeled with biotin, either in vivo by injection or in vitro. In vivo labeled red cells were followed up in some mice without transfusing the labeled erythrocytes. Furthermore, in vivo labeled as well as in vitro labeled red cells were transfused into syngeneic mice. The biotin label allows an easy discrimination between labeled and unlabeled red cells during FACS analysis, and it is relatively stable for at least 50 days. All the three different approaches give similar results. Mean red cell life spans of in vivo or in vitro labeled red cells either transfused or followed up in vivo were between 44 and 52 days (T50 mean 23.9 days) when red cell destruction was assumed to be only a result of senescence. Mean red cell life spans were between 8 and 18 days (T50 mean 9.5 days) when a random destruction independent of red cell age was suggested. All the survival slopes are neither simple linear functions of time nor logarithmic functions, but they show an overlay of linear function by a logarithmic function where the components of both are unknown.

T-cell subsets were studied by fluorescence-activated cell sorter analysis in 57 feline immunodeficiency virus (FIV)-seropositive cats with naturally acquired FIV infection to see whether CD4+-CD8+ alterations were comparable to those observed in human immunodeficiency virus-infected patients. CD4+ values were decreased and CD8+ values were increased. The CD4+/CD8+ ratio was reduced to 1.6, compared with 3.3 in 33 FIV-seronegative control cats. Variance analysis of data showed a significant influence of FIV seropositivity, sex, and spaying of female cats on CD4+ values. CD8+ values were significantly influenced by FIV seropositivity, age, and breed. These findings indicate a similarity between FIV and human immunodeficiency virus infections, as far as alterations of T-cell subsets are concerned. Feline immunodeficiency virus (FIV), first isolated in California (10), is a typical lentivirus that replicates preferably in feline T-lymphoblastoid cells and is structurally similar to human immunodeficiency virus (HIV). Experimental infection of cats induces transient fever, neutropenia, and lymphadenopathy. Following recovery from the initial phase, cats become lifelong carriers of the virus. One year or more after natural infection, cats may develop a terminal AIDS-like phase (12). Hematologic manifestations of FIV infection, including anemia, lymphopenia, neutropenia, and thrombocytopenia, as well as hyperplasia of individual cell lineages and dysmorphic features in bone marrow, are also similar to those in HIV-seropositive humans (14). Strong similarities between FIV infection and the human AIDS complex have been shown, not only in virus structure and clinical symptoms but also in epidemiological manifestations (12, 15). The human counterpart, HIV, is known to infect predominantly CD4+ T-helper lymphocytes and cells of the monocyte-macrophage lineage (3, 8; for a review, see reference 13). Gradual reduction in both the percentage and the absolute number of CD4+ T cells is one of the most striking immunological consequences of HIV infection. Recently, monoclonal antibodies (MAb) against cat CD4 (1) and CD8 (7) homologs have been developed. We have examined peripheral blood lymphocytes from FIV-positive domestic cats with naturally acquired infection (as judged by seroconversion) by using these anti-CD4 and anti-CD8 MAb. We found a variable reduction of CD4+ lymphocytes and an increased proportion of CD8+ lymphocytes in these cats, as already described in a brief report on 20 FIV-seropositive cats (5). MATERIALS AND METHODS Animals. Fifty-seven domestic cats found to be spontane

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Lymphatic organs of normo- and dysgammaglobulinemic chickens were studied by immunohistochemical methods concerning IgM-, IgG-, and IgA-positive cells. IgM- and IgA-positive lymphocytes and plasmacytic cells are similarly distributed in dys- and normogammaglobulinemic chickens. Follicles of the bursa of Fabricius contain cortical lymphocytes weakly and medullar lymphocytes distinctly stained by anti-IgM, as well as some larger irregularly shaped cells with intensely labeled cytoplasm. In spleen, periellipsoid lymphocytes, some red pulp lymphocytes, and varying numbers of plasmacytic cells are also distinctly labeled by anti-IgM. IgA-positive lymphocytes are not present in the bursa of Fabricius, but the bursal medulla is populated by some irregular, mostly longish cells with cytoplasmic IgA reaction. Spleen contains a few IgA-labeled lymphocytes and plasmacytic cells. The only difference between normo- and dysgammaglobulinemic chickens is found in IgG-positive cells, which are absent in permanently dysgammaglobulinemic chickens. The results from dysgammaglobulinemic chickens show that IgA can also be produced in untreated chickens lacking IgG synthesis and suggest that the theory of an IgM → IgG → IgA sequence is unlikely.