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IMMUNOLOGICAL MEMORY: Wake-up call

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The mechanism by which MHC signals preserve memory T-cell function still needs to be determined, but a new study calls for a re-evaluation of the role of MHC in maintaining T-Cell memory.

Fail to give a stimulating presentation and, although your audience might remain in their seats, chances are they will be unresponsive or even asleep. Does the same apply to memory T cells? Memory T cells don't seem to need MHC stimulation to stay alive, but a report from George Kassiotis and colleagues in Nature Immunology shows that they might need it to stay awake.

Recognition of self-peptide–MHC complexes by naive T cells triggers low levels of T-cell receptor (TCR) signalling. This gentle stimulation has been proposed to transmit a survival signal that is important for the maintenance of the naive T-cell pool. By contrast, memory T cells seem to survive just as well without MHC contact.

But do memory T cells that are deprived of MHC contact function normally? The authors used a TCR transgenic mouse system to test this. MHC class II-restricted T cells from TCR transgenic mice were transferred, together with antigen-pulsed dendritic cells (DCs), into lymphopenic hosts (recombinase activating gene 2^-/- common gamma chain^-/- mice) that expressed either normal levels of allogeneic MHC or no MHC class I/II at all. The transferred DCs prime the T cells then die, leaving no trace of antigen.

In agreement with previous studies, the monoclonal populations of transgenic memory T cells survived equally well in the absence of MHC contact, and in vitro responses to optimal stimuli (mature dendritic cells) were robust. However, the responses of memory T cells from MHC-negative hosts to suboptimal stimuli (resting B cells) were dramatically reduced. The authors confirmed that this defect was due to a requirement for MHC contact in the maintenance of memory T-cell function, rather than to a problem with memory T-cell formation in the MHC-negative hosts.

Is the defective function apparent in vivo? This was assessed in two ways. First, memory T cells were re-transferred into hosts in which only B cells could present antigen. Although the memory T cells derived from both the MHC-positive and MHC-negative hosts were activated by antigen, only those from MHC-positive hosts proliferated and provided 'help' for the B cells to produce antibody. Second, memory T cells were re-transferred into hosts (carrying allogeneic MHC molecules) that were subsequently given skin grafts. Only mice that had received T cells from MHC-positive hosts rejected the skin grafts, a response that depends on antigen presentation by DCs emigrating from the grafts.

The mechanism by which MHC signals preserve memory T-cell function still needs to be determined, but this study calls for a re-evaluation of the role of MHC in maintaining T-cell memory.

Jennifer Bell

References

ORIGINAL RESEARCH PAPER
Kassiotis, G. et al. Impairment of immunological memory in the absence of MHC despite survival of memory T cells. Nature Immunol. 3, 244–250 (2002). | Article | PubMed |
FURTHER READING
Swain, S. L. CD4 T-cell memory can persist in the absence of class II. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 355, 407–411 (2000). | PubMed |