Virus-specific CD8+ T-cell responses in mice transgenic for a T-cell receptor beta chain selected at random.
The consequences of severely limiting the T-cell receptor (TCR) repertoire available for the response to intranasal infection with an influenza A virus or with Sendai virus have been analyzed by using H-2k mice (TG8.1) transgenic for a TCR beta-chain gene (V beta 8.1D beta 2J beta 2.3C beta 2). Analyzing the prevalence of V beta 8.1+ CD8+ T cells in lymph node cultures from nontransgenic (non-TG) H-2k controls primed with either virus and then stimulated in vitro with the homologous virus or with anti-CD3 epsilon showed that this TCR is not normally selected from the CD8+ T-cell repertoire during these infections. However, the TG8.1 mice cleared both viruses and generated virus-specific effector cytotoxic T lymphocytes (CTL) and memory CTL precursors, though the responses were delayed compared with the non-TG controls. Depletion of the CD4+ T-cell subset had little effect on the course of influenza virus infection but substantially slowed the development of the Sendai virus-specific CTL response and virus elimination in both the TG8.1 and non-TG mice, indicating that CD4+ helpers are promoting the CD8+ T-cell response in the Sendai virus model. Even so, restricting the available T-cell repertoire to lymphocytes expressing a single TCR beta chain still allows sufficient TCR diversity for CD8+ T cells (acting in the presence or absence of the CD4+ subset) to limit infection with an influenza A virus and a parainfluenza type 1 virus.
Ewing
C
C
Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
Allan
W
W
Daly
K
K
Hou
S
S
Cole
G A
GA
Doherty
P C
PC
Blackman
M A
MA
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D006183:H-2 Antigens / Q000276:immunology; D006649:Histocompatibility Antigens / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology; D008657:Metabolic Clearance Rate; D051379:Mice; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000276:immunology; D010222:Parainfluenza Virus 1, Human / Q000276:immunology; D018184:Paramyxoviridae Infections / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D016827:CD8 Antigens; D006183:H-2 Antigens; D006649:Histocompatibility Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta