[Use of heat shock of antigen-presenting cells for functional testing of allospecificity memory T-cells].
For many years, the search for the appropriate method of testing the functional activity of the memory T-cells was an urgent problem and determined progress in the study of immunological memory. We proposed simple methods of functional testing the memory of CD8+ T-cells specific to the H-2Kb alloantigen based on measuring their proliferation in response to heat-treated allogenic splenocytes and cells of allogenic tumors in vitro. Primary proliferative response to the alloantigen was shown not to develop when the allogenic antigen-presenting cells were subjected to an acute (45 degrees C, 1 h) or moderate (42 degrees C, 30 min) heat shock. The block of the primary allogenic response of naive T-lymphocytes to the heated splenocytes could not be abrogated by the addition of exogenous IL-2 and was not due to deletion or suppression of antigen-reactive clones. On the contrary, the long-lived memory CD8+ T-cells induced in the course of the primary in vivo response were capable of proliferation in response to heat-treated allogenic stimulators carrying the same immunizing antigen. The different response of the naive T-cells and memory T-cells to the allogenic stimulators subjected to a heat shock might be due to a strict dependence of the naive T-cells on the inducing co-stimulation provided by the B7 ligand, whose expression was suppressed in the cultures containing the heat-treated stimulator cells. These results probably suggest that a specific immunoregulatory mechanism exists that is based on a disorder in costimulatory functions due to the cellular stress-response induced in the antigen-presenting cells.
Kazanskiĭ
D B
DB
Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow, Russia. kazansky@dataforce.net
Petrishchev
V N
VN
Shtil'
A A
AA
Chernysheva
A D
AD
Sernova
N V
NV
Abronina
I F
IF
Pobezinskiĭ
L A
LA
Agafonova
E L
EL
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D017931:DNA Primers; D006183:H-2 Antigens / Q000276:immunology; D018869:Heat-Shock Response; D007156:Immunologic Memory; D051379:Mice; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse