Lymphocyte function and virus infections.

Lymphocytes in the blood and central lymphoid tissues participate in a variety of host defence mechanisms against virus infections. These include cell-mediated reactions against infected cells and particularly those involving cytotoxic T lymphocytes, co-operation in the induction of antibody responses, and the production of immune interferon. During the early stages of many virus infections the invading virus replicates in lymphoreticular cells, and this is of advantage to the host because of the increased efficiency with which the resulting immune responses are induced. Indeed, in many virus infections of man viral antigens can readily be detected in circulating blood lymphocytes. Nevertheless, this association with lymphocytes does not always benefit the host and may increase the virulence of the virus and enhance its persistence. There are many examples of experimental virus infections in which this train of events has been observed. For example, in inbred mouse strains infected with lymphocytic choriomeningitis (LCM) virus, either by intracerebral injection at birth or congenital in-utero infection, virus can be detected in all the major subpopulations of mononuclear cells-namely, T lymphocytes, B lymphocytes, and cells of the monocyte-macrophage series (Doyle and Oldstone, 1978). This infection of mononuclear cells of the peripheral and central lymphoid system persists throughout the life of the animal. It has also been suggested that by infecting lymphocytes the virus may on occasion prevent the induction of an appropriate immune response to the infecting agent. This suppression may be more likely if the host is infected at a time of immunological immaturity determined by the age at which the animal is infected or by other factors that have a general immunosuppressive effect. In other words, the virus may delete precisely that clone of reactive cells which is programmed to respond to the invading agent. Another undesirable consequence of lymphocyte infection is the dissemination of virus in association with cells. It has been proposed, for example, that canine distemper virus enters the central nervous system in this manner (Summers et al., 1978). To demonstrate that similar considerations apply to 39 human infections by pathogenic viruses is obviously more difficult. However, the damage to the immune system that may accompany congenital rubella infection is a clear indication that the same principles apply. Moreover, transient immunosuppression accompanies many virus infections of man. There are now precise means of examining the interactions between different viruses and human lymphocytes, and the findings of such experiments are reviewed in this paper. The results are considered in two waysfirstly, the effects of virus infection on lymphocyte function and, secondly, the effects of residence in lymphocytes on the biological properties of viruses.