T Cell Memory

Abstract

Immunological memory can be defined as the faster and stronger response of an animal that follows reexposure to the same antigen. By this definition, it is an operational property of the whole animal or the immune system. Memory cells express a different pattern of cell surface markers, and they respond in several ways that are functionally different from those of naive cells. Murine memory cells are CD44 high and low in the expression of activation markers such as CD25 (IL-2R), whereas human memory cells are CD45RA-, CD45RO+. In contrast to naive cells, memory cells secrete a full range of T cell cytokines and can be polarized to secrete particular restricted patterns of secretion for both CD4 and CD8 T cells. The requirements for the activation of memory cells for proliferation and cytokine production are not quite as strict as those of naive cells, but costimulation in the broad sense is required for optimum responses and for responses to suboptimum antigen concentrations. It would appear that memory cells can persist in the absence of antigenic stimulation and persist as nondividing cells. Reencounter with the same antigen can expand the population to a new, stable, higher level and generate a separate population of CD44 high effectors that may be required for protection, while competition from other antigens can drive it down to a lower stable level. It is unclear how or where memory cells arise, but once generated they have different pathways of recirculation and homing.

Primed Allospecific T Cells Prevent the Effects of Costimulatory Blockade on Prolonged Cardiac Allograft Survival in Mice

“…Studies by Kupiec-Weglinski and colleagues using models of accelerated cardiac and renal allograft rejection in sensitized rats have in fact shown that tolerance can be induced under some conditions despite the presence of primed, effector T cells (42). It is important to note that in contrast to our studies, these previously published experiments generally involved treatment within 1 week of the skin graft sensitization, a time-point at which the primed T cells are likely to have an effector phenotype that may have different susceptibilities to costimulatory blockade than a memory cells (22,36). Moreover, these investigators used alternate reagents (CTLA4Ig vs. aCD40L) and, notably, did not induce prolonged graft survival in the majority of the animals.…”

“…CD40 binding to CD40L is known to be an important costimulatory signal for the activation of naïve T cells, and antigen recognition by naïve T cells in the absence of costimulation has been shown to actively induce a tolerant state (12)(13)(14). In contrast to naïve T cells, however, antigen-experi-enced T cells have lower costimulatory requirements for activation, and may become activated in the total absence of costimulation, particularly if the T-cell receptor MHC-peptide interaction is of high affinity (21,22,35,36). In addition, while there is some evidence to suggest that naïve CD8π T cells are deleted following DST/aCD40L therapy (17), it is clear that memory T cells up-regulate the expression of antiapoptotic genes such as bcl-2 and are known to be resistant to activation-induced cell death (37)(38)(39).…”

In vitro generated human memory‐like T cells are CD95 type II cells and resistant towards CD95‐mediated apoptosis

“…Immune reactions usually lead to immunological memory in form of persisting memory cells. These ensure a quick specific and effective response upon a secondary encounter of antigen (for review see [16,17]). Compared to naive T cells memory T cells generate faster and more effective responses at low doses of antigen [18].…”

A stochastic model of cytotoxic T cell responses

“…Memory cells are able to mount a quicker and more aggressive response in future encounters with the same or closely related pathogens (Dutton et al, 1998). This secondary response can clear an infection before significant damage is inflicted upon the body.…”

“…New memory cells from heterologous infections can displace the memory cells from responses to prior infections (Selin et al, 1996;McNally et al, 2001). In the absence of immune system challenges, memory cells turn over slowly (Dutton et al, 1998;Murali-Krishna et al, 1999).…”