Influence of T Cell Coinhibitory Molecules on CD8+ Recall Responses

Abstract

T cell co-signaling molecules play an important role in fine-tuning the strength of T cell activation during many types of immune responses, including infection, cancer, transplant rejection, and autoimmunity. Over the last few decades, intense research into these cosignaling molecules has provided rich evidence to suggest that cosignaling molecules may be harnessed for the treatment of immune-related diseases. In particular, coinhibitory molecules such as programmed-death 1, 2B4, BTLA, TIGIT, LAG-3, TIM-3, and CTLA-4 inhibit T cell responses by counteracting TCR and costimulatory signals, leading to the inhibition of proliferation and effector function and the downregulation of activation and adhesion molecules at the cell surface. While many reviews have focused on the role of coinhibitory molecules in modifying primary CD8+ T cell responses, in this review, we will consider the complex role of coinhibitory molecules in altering CD8+ T cell recall potential. As memory CD8+ T cell responses are critical for protective memory responses in infection and cancer and contribute to potentially pathogenic memory responses in transplant rejection and autoimmunity, understanding the role of coinhibitory receptor control of memory T cells may illuminate important aspects of therapeutically targeting these pathways.

Inhibitory checkpoint receptors control CD8+ resident memory T cells to prevent skin allergy

“…In this respect we investigated expression of different ICRs by skin CD8 1 Trm cells. 22 We noticed that these cells expressed high levels of PD-1, 23 TIM-3, 24 or 2B4 (Fig 3, B), 25 as well as CD5, 26 but not T cell immunoreceptor with Ig and ITIM domains (TI-GIT), 27 Of note, the number of DNFB-specific IFN-g-producing T cells among CD8 1 PD-1 1 Trm cells was 2 times higher compared with that in their PD-1 2 counterparts, as revealed by using an ELISpot assay at day 30 The following day, the number of specific T cells was determined by using an IFN-g ELISpot assay. Results are expressed as mean 6 SEM numbers of spot-forming cells/10 6 CD8 1 T cells.…”

Advances in Understanding the Roles of CD244 (SLAMF4) in Immune Regulation and Associated Diseases

“…Moreover, addition of CD244 to wild-type NK cells inhibited cell toxicity and IFN production, and the same inhibitory effect occurred in memory CD8 + T cells. In chronic infections, CD244 limited the recall response of CD8 + T cells by inhibiting their proliferation and function ( 37 ). The reason for these different results may be that CD244 binds to multiple protein receptors that transmit different intracellular signals.…”

Aging boosts antiviral CD8+T cell memory through improved engagement of diversified recall response determinants

“…In contrast to the wealth of information detailing the roles of multiple TCR-independent determinants in shaping I o pathogen-specific CD8 + T E responses, considerably less information is available about the regulation of II o CD8 + T E immunity [72, 73]. Moreover, the notion of long-term CD8 + T cell memory as a progressively evolving trait has gained increasing traction over the past half decade and implies the potential remodeling of relevant recall response determinants; to date, however, their identities and possible contributions to altered II o CD8 + T E reactivity remain largely unknown.…”