Effect of helper T cells on the primary in vitro production of delayed-type hypersensitivity to influenza virus.

Abstract

Injection of mice with infectious or noninfectious preparations of influenza virus induces the formation of T cells which, when added to primary tissue cultures of normal spleen cells exposed to influenza virus, enhance the generation of effector T cells which mediate delayed-type hypersensitivity (DTH) reaction. The enhancing cells possess Thy-1 and Ly-1 surface antigens are radioresistant and antigen-specific. If infectious virus was used to stimulate the DTH response in vitro, help was delivered whether homologous or heterologous A strain influenza virus was used to generate the helper T cells (Th) in vivo. In contrast, only Th cells generated using homologous virus were effective if noninfectious virus was used to stimulate the DTH response in vitro. Peak helper activity occurred 2 d after virus injection and the Th cells were only effective if added to the primary cultures within 24 h after addition of the stimulating antigen. The Th cells enhanced the generation of both classes of DTH effector cells, i.e., those that are Ly-1 positive and IA-subregion restricted and those that are Ly-2,3 positive and K,D-region restricted. The activity of the Th cells was found to be IA-subregion restricted and this was shown to operate at the level of the stimulator cells so that the delivery of help to the responder cells was not H-2 restricted. The possibility that the Th cells might be a precursor to the Ly-1 positive IA subregion-restricted DTH effector cells is discussed.

Protection of mice from lethal influenza by defective interfering virus: T cell responses

“…Therefore it would appear that preexisting CTLs protect against infection, whereas those generated during infection are pathogenic. Finally our data and those of others agree that delayed type hypersensitivitymediating and/or CD4 ÷ T cells, whether administered before infection or generated during the course of it, can be pathogenic in the influenza virus-infected mouse (Leung & Ada, 1980, 1982Liew & Russell, 1980, although other data show them to be marginally beneficial (Lukacher et al, 1986;Askonas et al, 1988). In conclusion, our data clearly show the immunopathogenic contribution of T cells during fatal influenza pneumonia in the mouse.…”

Vaccines for the Future?

“…The first specific response we have detected (Ada et al, 1981) is the presence of specific T helper (Th) cells which also reach maximum levels of activity 2-3 days after inoculation of virus. Their activity was detected as an enhancement in the generation of delayed-type hypersensitivity (DTH) in an in vitro system, and presumably the same set of cells or similar sets act as Th cells for other lymphocyte responses.…”

“…Injection of inactivated HI virus will generate neutralizing antibody of that speciflcity only and both the Th and Td cells generated will also display that specificity. If infectious HI virus is used, the neutralizing antibody generated will also be specific, but the T cells generated, Th, Td (Ada et al, 1981) and Tc will show marked crossreactivity between all sero subtypes (Doherty, Effros and Bennink, 1977). In fact, most clones of Tc cells generated will be cross-reactive (Owen, Allouche and Doherty, 1982).…”

“…Macrophages recovered from the mouse lung do not support productive replication of influenza virus (Rodgers and Mims, 1981) so a major role is to act as a scavenger cell. They may also act as antigenpresenting cells (Ada et al, 1981). Mice which carry the Mx allele are remarkably resistant to infection by orthomyxovimses and this has been shown to be due to activation of macrophages in these mice by low levels of interferon (Haller, 1980).…”

Differences in the phenotypes of cells mediating anti‐tumour immunity at various stages of tumour progression in mice

“…Even in the containment and destruction of viruses, in which it has long been established that Ly 1 -(low)2+ cytotoxic T cells have a key role, T cells mediating responses similar to DTH are also critical (41), acting as amplifiers of the immune response (42). In the MC-2 model, co-operation between Ly 2+ and Ly 2~ cells does not appear to be critical in animals with strong anti-tumour immunity.…”