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Forty-two kittens and 28 adult cats were placed as tracers in leukemia cluster environments in contact with resident cats, 30% of which were persistently infected with feline leukemia virus (FeLV). After 7 months exposure, FeLV viremia had been detected in 71% of the tracer kittens, although only 55% of these remained persistently infected; in the same period, 11% of tracer adults became infected, but by 2 years the figure reached 43%. Mean latent periods before detection of viremia were 3.4 +/- 1.8 (S.D.) and 13.0 +/- 5.9 months for kittens and adults, respectively. First detection of FeLV infection was accompanied by a sharp although transient drop in peripheral white blood cell numbers, and infection onset triggered the humoral immune response which was comprised of separate antibodies with virus-neutralizing and tumor lysis activities. High titers of virus-neutralizing antibody appeared in transiently viremic cats immediately following elimination of viremia; this antibody was rarely detected in cats that remained persistently viremic. Lytic complement-dependent antibody to feline oncornavirus-associated cell membrane antigen appeared in most cats 1 to 2 weeks after FeLV infection was first detected, and subsequently high titers of this antibody remained in both transiently and persistently infected cats. If the rate of FeLV infection was summarized by using viremia and/or antibody appearance, then 95% of the kittens became infected within 1 year and 61% of the adults within 2 years. Adult cats are, therefore, susceptible to FeLV infection following long-term natural exposure, and their apparent resistance cannot be attributed to a protective humoral immune response that developed immediately after exposure commenced.

One hundred eighty-four cases of feline leukemia and lymphoma diagnosed in Boston from 1972 through 1976 were investigated. Fifty-eight % of these cases were lymphoma, and 42% were leukemia. Sixty-seven % of the cats had positive fluorescent antibody tests for circulating feline leukemia virus. The rest (33%) were virus negative. Clinically and epidemiologically, the virus-positive and virus-negative cases were remarkably similar except for their age at diagnosis. Virus-negative cats tended to be older (mean age at diagnosis, 4.9 years) as compared to virus-positive cats (3.5 years). For 22 cases of leukemia and lymphoma diagnosed after the age of 8 years, 15 were virus negative. The minimum mean induction period (time from first positive virus test to diagnosis of cancer) for 19 cats that were virus positive and healthy at their first test was 16.7 months (range, 2 to 41 months).

The immunological and cytochemical phenotypes of five primary feline lymphomas and six feline lymphoma lines are reported. Thymic lymphomas induced by the Rickard strain of FeLV (FeLV-R) are of prothymocyte or (immature) cortical thymocyte origin, as these express terminal deoxynucleotidyl transferase, the guinea pig erythrocyte rosette receptor, Ia antigens, partial cortisone sensitivity, and nonspecific esterase. Lymphomas associated with other strains of FeLV form rosettes with guinea pig erythrocytes, frequently have Ia antigens and cytoplasmic nonspecific esterase, and probably originate from helper T-cells, monocyte/macrophages, or null cells. These data belie previous conclusions that FeLV leukemogenesis is restricted to mature T-cells; rather, the considerable heterogeneity in the surface and cytochemical phenotype of feline lymphomas probably reflects transformation of multipotent lymphoid or monocytoid precursors in the bone marrow by FeLV.

The feline leukemia virus (FeLV) was discovered in 1964 in a cluster of cats with lymphosarcoma. The observed clustering of cases of feline lymphosarcoma suggested that FeLV was an infectious agent for cats. The development of a simple immunofluorescent test for FeLV permitted a seroepidemiological study to be undertaken on the distribution of the virus in cats living in their natural environment. Over 2000 cats were tested, and the results showed conclusively that FeLV is an infectious agent for cats. This finding has now been independently confirmed using three different test procedures. After the infectious nature of FeLV was discovered, a simple FeLV test and removal program was devised to control the spread of the virus in the natural environment. The spread of FeLV was controlled in 45 households by removing the FeLV-infected cats, while in 25 households, where the infected cats were left in contact with the uninfected cats, 12% of the uninfected cats became infected. The ultimate control of FeLV awaits the development of an effective FeLV vaccine, which now seems feasible since we have already experimentally immunized some cats with attenuated FeLV. Although FeLV is infectious for cats there is no evidence that FeLV can infect humans.

Cats represent an unusually valuable model for studying the role of the immune response to leukemia, lymphoma, and other mesodermal neoplasms. The agents that cause spontaneous feline leukemias, lymphomas, and fibrosarcomas, the feline leukemia and sarcoma viruses, are well characterized. A specific tumor cell membrane antigen, designated the feline oncornavirus-associated cell membrane antigen (FOCMA) has also been described. Feline leukemia and feline sarcoma viruses are antigenically indistinguishable, and FOCMA is common for both. Both laboratory-induced and spontaneous feline leukemias, lymphomas, and fibrosarcomas are available for study. A clear correlation has been shown between the resistance of cats to development of lethal tumors following inoculation of feline sarcoma virus and the presence of high humoral antibody titers to FOCMA. The geometric mean antibody titer to FOCMA for cats that resisted growth of fibrosarcomas was more than 20-fold higher than the mean for cats that succumbed to lethally progressing tumors. Cats with induced or spontaneous leukemia or lymphoma also have either no detectable FOCMA antibody or very low levels. Conversely, some cats resist development of leukemia or lymphoma following natural exposure to feline leukemia virus in leukemia cluster households, and these cats have high FOCMA antibody titers. These results support the concept of a natural immunosurveillance mechanism against leukemia or lymphoma development in an outbred mammalian species.