Induction of antigen-specific CD8+ cytolytic T cells by the exogenous bacterial antigen streptolysin O in rhesus monkeys.
We have characterized the T cell responses induced by streptolysin O (SLO), a sulfhydryl-activated hemolysin secreted by streptococci, by applying long-term in vitro culture and cloning rhesus monkey (Macaca mulatta) T cells. T cell lines specific for SLO were obtained from three rhesus monkeys. These T cell lines required autologous antigen-presenting cells (APC) to proliferate in response to SLO and did not respond to purified protein derivative. Phenotypic analysis showed that the cells from two of three SLO-specific T cell lines were more than 85% CD3+CD4-CD8+ after prolonged in vitro culture. The rh 1842 CD8+ T cell line proliferative response to SLO was inhibited by the addition of anti-major histocompatibility complex (MHC) class I and anti-CD8 but not of anti-MHC class II and anti-CD4 monoclonal antibody (mAb). This cell line was able to lyse P815 target cells in the presence of anti-CD3 mAb and did not show natural killer activity. Moreover, specific lysis of autologous but not allogeneic non-rosetting E- cell targets pulsed with SLO was observed. Such lysis was inhibited by the addition of anti-MHC class I mAb. In the attempt to identify the restriction elements involved in SLO presentation APC from six unrelated rhesus monkeys and three humans were used. A CD4+ rh 1842 T cell clone responded when SLO was presented by one of six, and a CD8+ rh 1842 T cell clone by four of six rhesus monkeys APC. Both CD4+ and CD8+ T cell clones did not respond when SLO was presented by human APC. However, both clones responded when APC from all donors were used in conjunction with anti-CD3 mb. Furthermore, SLO required active processing to be presented to CD4+ and CD8+ T cell clones as glutaraldehyde fixation of APC before but not after antigen pulsing inhibited T cell proliferation. The SLO-specific CD8+ cytolytic T cells described here could play a role in the regulation of the immune response occurring during streptococcal infections and/or could participate in the pathogenesis of poststreptococcal nonsuppurative sequelae.
Chizzolini
C
C
Division of Parasitic Diseases, Public Health Service, U.S. Department of Health and Human Services, Atlanta.
Millet
P G
PG
Olsen-Rasmussen
M A
MA
Collins
W E
WE
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D008213:Lymphocyte Activation; D008253:Macaca mulatta / Q000276:immunology*; D008285:Major Histocompatibility Complex; D013301:Streptolysins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016827:CD8 Antigens; D013301:Streptolysins; C025964:streptolysin O