Preproinsulin specific CD8Â + T cells in subjects with latent autoimmune diabetes show lower frequency and different pathophysiological characteristics than those with type 1 diabetes

•Subjects with T1D had higher frequency of PPI specific CD8 + T cells in their peripheral blood as compared to LADA subjects•Majority of PPI specific CD8 + T cells were of effector phenotype in T1D group and effector-memory phenotype in LADA group.•PPI specific autoreactive CD8 + T cells in LADA subjects have inferior proliferative potential.•PPI specific central-memory CD8+ T cells increase upon in-vitro stimulation with PPI in T1D but not in LADA subjects.

Latent autoimmune diabetes in adults (LADA) resembles type 1 diabetes (T1D) in disease presentation except that its onset is slow. We compared pathophysiological characteristics of CD8 + T cells recognizing preproinsulin (PPI) derived epitopes in both disease groups using MHC-I dextramers (DMRs) in peripheral blood and after in-vitro stimulation with PPI. Subjects with T1D harbored higher frequency of DMR + CD8 + T cells with relatively higher frequency of effector T cell subsets. Following stimulation with PPI, an increase in DMR + CD8 + T cells, particularly the central-memory subset was observed in T1D group, whereas no significant change in DMR + CD8 + T cell subsets was observed in LADA group. Intracellular expression of Granzyme-B and Perforin in DMR + CD8 + T cells was comparable in both the groups. In conclusion, lower frequency and inferior proliferative potential on account of a relatively restrained central-memory subset of PPI specific CD8 + T cells are associated with slow rate of disease progression in LADA.