title: Differentiation of CD8+ T cells into effector cells is enhanced by physiological range hyperthermia.
abstract: In this study, we asked whether exposure to different physiologically relevant temperatures (33°C, 37°C, and 39.5°C) could affect subsequent antigen-specific, activation-related events of naive CD8(+) T cells. We observed that temporary exposure of CD62L(hi)CD44(lo) Pmel-1 CD8(+) cells to 39.5°C prior to their antigen-dependent activation with gp100(25-33) peptide-pulsed C57BL/6 splenocytes resulted in a greater percentage of cells, which eventually differentiated into CD62L(lo)CD44(hi) effector cells compared with cells incubated at 33°C and 37°C. However, the proliferation rate of naive CD8(+) T cells was not affected by mild heating. While exploring these effects further, we observed that mild heating of CD8(+) T cells resulted in the reversible clustering of GM1(+) CD-microdomains in the plasma membrane. This could be attributable to a decrease in line tension in the plasma membrane, as we also observed an increase in membrane fluidity at higher temperatures. Importantly, this same clustering phenomenon was observed in CD8(+) T cells isolated from spleen, LNs, and peripheral blood following mild whole-body heating of mice. Further, we observed that mild heating also resulted in the clustering of TCRβ and the CD8 coreceptor but not CD71R. Finally, we observed an enhanced rate of antigen-specific conjugate formation with APCs following mild heating, which could account for the difference in the extent of differentiation. Overall, these novel findings may help us to further understand the impact of physiologically relevant temperature shifts on the regulation of antigen-specific CD8(+) T cell activation and the subsequent generation of effector cells.
authors.affiliation: Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Mace
authors.forename: Lingwen
authors.initials: L
authors.lastname: Zhong
authors.forename: Casey
authors.initials: C
authors.lastname: Kilpatrick
authors.forename: Evan
authors.initials: E
authors.lastname: Zynda
authors.forename: Chen-Ting
authors.initials: CT
authors.lastname: Lee
authors.forename: Maegan
authors.initials: M
authors.lastname: Capitano
authors.forename: Hans
authors.initials: H
authors.lastname: Minderman
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Repasky
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D005334:Fever / Q000276:immunology; D005677:G(M1) Ganglioside / Q000276:immunology; D018960:Hyaluronan Receptors / Q000276:immunology; D019041:L-Selectin / Q000276:immunology; D008213:Lymphocyte Activation / Q000502:physiology*; D021962:Membrane Microdomains / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013696:Temperature; D058951:gp100 Melanoma Antigen / Q000276:immunology
chemical_list: C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; D010455:Peptides; D058951:gp100 Melanoma Antigen; D019041:L-Selectin; D005677:G(M1) Ganglioside