Upregulation and induction of major histocompatibility complex class I and II antigens on microglial cells in early postnatal rat brain following intraperitoneal injections of recombinant interferon-gamma

Abstract

Interferon-γ when given intraperitoneally by single daily injection into one-day-old rats upregulated the expression of major histocompatibility complex class I antigen on ramified microglial cells in cerebral cortex and induced the expression of major histocompatibility complex class II antigen both on amoeboid and ramified microglial cells present in corpus callosum and cerebral cortex, respectively. In rats receiving single daily injections of interferon-y over a period of three consecutive days and killed at the age of seven days, the endothelium exhibited a moderate to weak immunoreaction for major histocompatibility complex class I antigen as detected with the monoclonal antibody OX-18. The immunoreactivity of major histocompatibility complex class I antigen on amoeboid microglial cells was comparable to that of control rats. On the other hand, it was remarkably enhanced on ramified microglial cells and was further intensified with four or six injections of interferon-γ. In the latter, the endothelial cells also showed a stronger immunoreactivity with OX-18. In rats given three successive injections of interferon-γ and killed at the age of seven days, 7.5% of amoeboid microglial cells in corpus callosum were induced to exhibit major histocompatibility complex class II antigen as detected with OX-6. An upsurge of the amoeboid microglial cells with major histocompatibility complex class II antigen amounting to about 40% was observed following four and six injections of interferon-y. A minimum of four successive injections of interferon-y were needed to elicit the expression of major histocompatibility complex class II antigen on ramified microglial cells in cerebral cortex. With six injections, a larger number of ramified microglial cells were provoked to express major histocompatibility complex class II antigen. In rats receiving four or six successive injections of interferon-γ and killed at 14 and 21 days of age, the immunoreactivity for major histocompatibility complex class I and II antigens on microglial cells was comparable to that of control rats. Results in this study showed that the expression of major histocompatibility complex class II antigen on amoeboid microglial cells was more readily elicited by interferon-γ than that on ramified microglial cells. Their differential response to interferon-γ may be related to their different degree of maturation; it may also be attributed to the different stages of development of blood-brain barrier in their microenvironments. It is suggested from the present study that the upregulation and induction of major histocompatibility complex class I and class II antigens on amoeboid microglial cells and ramified microglial cells by interferon-γ in early postnatal rat brain may trigger off the immunological potentiality of these cells to initiate a possible immune response.