Gamma interferon production in response to homologous and heterologous strain antigens in mice chronically infected with Rickettsia tsutsugamushi

Abstract

The ability of antigen-responsive, thymus-derived lymphocytes to produce immune (gamma) interferon was investigated during the development and expression of cellular immunity to Rickettsia tsutsugamushi. C3H/HeDub mice infected subcutaneously with the Gilliam strain developed the ability to produce serum interferon in response to intravenously inoculated antigen which correlated with the development of resistance to intraperitoneal rechallenge. Antigen-responsive lymphocytes, measured by interferon production and proliferation, were first apparent in draining lymph node cells, but spleen cell responses were detectable relatively soon after the appearance of reactive lymph node cells. The peak spleen cell response was of a greater magnitude and was found to be relatively long-lived. Reactivity to heterologous strains of R. tsutsugamushi also developed after immunization and paralleled the homologous responses, although reactivity was greatest to homologous antigens. Responses to heterologous strains differed in magnitude and time of appearances; however, immune mice resisted challenge with all strains of R. tsutsugamushi tested.

Immunosuppression associated with the development of chronic infections with Rickettsia tsutsugamushi: adherent suppressor cell activity and macrophage activation

“…Although the antibody response to TNP-Ficoll has recently been shown to be influenced by T-cells (21,22), they are not obligatory. The responses to SRBC, however, require T-cells and the differences in the magnitude of suppression of these different types of antigen suggests a more profound influence on T-cell function following rickettsial infection, In this study, it was noted that s.c. infection was associated with a marked influx of inflammatory macrophages into the spleen which probably is a consequence of rickettsial spread from the s.c. site of infection to systemic sites as has been previously suggested by rickettsial recovery from the blood and spleen (17,32), induction of Ia-antigen bearing macrophages in the peritoneal cavity (11), and the appearance of systemic immunity (9,15,17,28,33) following an s.c. infection. The suggestion that this influx was a result of an immune response to rickettsiae in the spleen is further supported by the demonstration that the adherent cell population obtained at the height of the inflammatory influx contained activated macrophages as measured by tumor cell cytotoxicity and antirickettsial activity.…”

“…The suggestion that this influx was a result of an immune response to rickettsiae in the spleen is further supported by the demonstration that the adherent cell population obtained at the height of the inflammatory influx contained activated macrophages as measured by tumor cell cytotoxicity and antirickettsial activity. Although there are insufficient data in this study to establish that this activation is a result of a specific immune response, other studies have shown that antigen-responsive cells are present at this time (15,28), and it is likely that the activation is the result of gamma interferon or other mediator production by antigenspecific lymphocytes in response to rickettsiae in the spleen as has been shown with in vitro methods (23). In a recent study similar data were obtained by Nacy and Meltzer (24), using macrophages obtained from Ricr mice which were recovering from an i.p.…”

“…This chronic infection is thought to persist for the life of the animal, suggesting that the rickettsiae are able to survive in the face of an immune response which is demonstrable at the same times (16,32,33). The immunity which develops in response to infection consists of a cell-mediated immunity as measured by a delayed-type hypersensitivity (15), antigen-induced lymphocyte proliferation (16), lymphokine production (27,28), and the development of lymphocytes capable of transferring protective immunity to naive animals (33), as well as a T-dependent antibody response (13).…”

Interferon‐gamma and resistance to bacterial infections

“…A role for IFN-)I in immune resistance to rickettsia infection is suggested by the demonstration of IFN-y production in mice in response to challenge with R. tsutsugamushi and the correlation between peak IFN-y responses and clearance of rickettsemia (87,88). In addition, administration of monoclonal antibody raised against MuIFN-y to mice infected with R. conorii has been shown to exacerbate infection (6 1).…”

Induction of Protective Immunity Against Scrub Typhus With a 56-Kilodalton Recombinant Antigen Fused With a 47-Kilodalton Antigen of Orientia Tsutsugamushi Karp

“…32 This has been demonstrated by passive transfer of resistance with T cells, 33 development of DTH, 34 and in vitro cytokine secretion of T cells in response to O. tsutsugamushi antigens. 10,11,13,35 Th1 cells have been shown to be responsible for the DTH response, which has been found to correlate with resistance to lethal challenge in mice infected with scrub typhus. 34,36 The proliferative level of splenic cells from mice immunized with Sta56-47 antigen was much higher than that in Sta56-or Sta47-immunized mice in response to homologous antigens.…”