Induction of cytotoxic T-cell responses in vivo in the absence of CD4 helper cells

Abstract

Cytotoxic T lymphocytes (CTL) seem to provide the major line of defence against many viruses. CTL effector functions are mediated primarily by cells carrying the CD8 (Ly-2) antigen (CD8+ cells) and are triggered by interactions of the T-cell receptor with an antigenic complex, often termed 'self plus X', composed of viral determinants in association with class I molecules of the major histocompatibility complex (MHC). The mechanism(s) of induction of virus-specific CTL in vivo is poorly understood, but data from in vitro experiments suggest that their generation is strictly dependent on functions provided by CD4+ helper T cells (also referred to as L3T4+; or TH) that respond to antigens in the context of class II (Ia) MHC determinants. The prevailing opinion that induction of most functions of CD8+ cells requires help provided by CD4+ cells has recently been challenged by the observation that CD8+ cells alone can mediate a variety of responses to alloantigens in vitro and in vivo; however, the possibility that CTL to self plus X could be generated in vivo in the absence of TH cells has not been evaluated. We report here that C57BL/6J (B6) and AKR/J mice, when functionally depleted of CD4+ cells by in vivo treatment with the CD4+-specific rat monoclonal antibody GK1.5 (refs 8-14) responded to ectromelia virus infection by developing an optimal in vivo virus-specific CTL response, and subsequently recovered from the disease (mousepox) that was lethal for similarly infected nude mice (CD4-, CD8-).

Poxvirus as a vector to transduce human dendritic cells for immunotherapy: abortive infection but reduced APC function

“…First, experiments in animal models have shown that CD4 + helper cells are not required for an anti-VV CTL response. 55 Furthermore, CTL responses to VV and other viruses have been observed in CTLA-4 transgenic mice, suggesting that CD80 expression by APC is not an absolute requirement for the induction of a CTL response. 56,57 In addition, it has been shown that the costimulatory molecule CD86 (which was not affected by VV, Figure 5) can drive a CTL response in a MHC restricted manner.…”

Site-restricted persistent cytomegalovirus infection after selective long-term depletion of CD4+ T lymphocytes.

“…Since, however, after long-term depletion of the CD4 subset, the lymphocyte population was composed of a CD8 subset and of a new subset with the phenotype CD4-CD8-(recall Fig. 2), it became necessary to also consider the possibility that the antiviral function was performed by this new subset and not, as one would anticipate from published experience (19)(20)(21)(22), by CD8' effector cells generated independently of the CD4 subset . Elimination in vitro of the CD8 subset and transfer of the resulting purified CD4-CD8-population (Fig.…”

“…Recent reports have given examples for an autonomy in vivo of the CD8 subset in viral infection models involving a depletion of the CD4 subset (19)(20)(21)(22), which implies that cooperation of CD4+ helper T lymphocytes is not essential for initiating a CD8 subset-mediated immune response. Whether such a response can last long enough to also maintain a long-term control and eosin.…”

Suppression of murine tumour growth through CD8+ cytotoxic T lymphocytes via activated DEC‐205+ dendritic cells by sequential administration of α‐galactosylceramide in vivo

“…The most effective cells for eliminating tumour cells are CD8 + cytotoxic T lymphocytes (CTLs) that specifically recognize the tumour antigens presented in association with class I MHC molecules 1. To prime and activate CTLs in a tumour environment, dendritic cells (DCs) are key cells that uptake tumour proteins, process them into peptide fragments containing immunodominant epitope(s), and present them on their surface associated with antigen‐presenting class I MHC molecule(s) for the activation of specific T‐cell immunity 2, 3…”