APC-dependent impairment of T cell proliferation in aging: role of CD28- and IL-12/IL-15-mediated signaling.
The age-related impairment of phytohaemagglutinin (PHA)-triggered peripheral blood mononuclear cell (PBMC) proliferation was paralleled by an expansion of CD28 (-) T lymphocytes with a poor capacity to undergo lectin-induced blastogenesis. However, both CD28 (-) and CD28 (+) T cells isolated from aged individuals exhibited a significant reduction of proliferative response to PHA in comparison with young controls, this implies that the CD28-mediated signaling is not the only defective pathway in the elderly. Thus, PBMC or T cell subsets plus monocytes from aged donors were stimulated with PHA and assayed for the production of, or the response to cytokines known to regulate T cell functions. Results can be so summarized: (i). interleukin (IL)-2 as well as IL-10 release was unaffected by age; (ii). in both groups of subjects, IL-15 concentrations were similar to those spontaneously released by PBMC; (iii). surprisingly, IL-12 p70 and IL-12 p40 production by PBMC was markedly increased in the aged group; (iv) in spite of this finding and of the experimental outcome that IFN-gamma synthesis was almost completely dependent on IL-12. PBMC from old individuals did not release higher amounts of IFN-gamma in comparison with young controls; (v). moreover, only a slight increase in IFN-gamma production was observed in PBMC cultures from the aged group as a result of IL-12 and/or IL-15 costimulation; (vi) at the same time, even though IL-12 as well as IL-15 were necessary for an efficient T cell proliferation, the addition of exceeding doses of cytokines proved to be ineffective in enhancing the proliferative outcome of PBMC or of both CD28 (+) and CD28 (-) T cells in the aged group. Taken together, the data outline the role of CD28 and IL-12/IL-15 signaling impairment in T cell proliferative deficiency during senescence.
Tortorella
Cosimo
C
Department of Internal Medicine, Immunology and Infectious Diseases, Section of Internal Medicine, University of Bari Medical School, Clinica Medica II, Policlinico, 70124, Bari, Italy. c.tortorella@intmed.uniba.it
Pisconti
Addolorata
A
Piazzolla
Giuseppina
G
Antonaci
Salvatore
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology*; D002455:Cell Division; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology*; D019409:Interleukin-15 / Q000096:biosynthesis / Q000276:immunology*; D007376:Interleukin-2 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D018106:CD28 Antigens; D019409:Interleukin-15; D007376:Interleukin-2; D010835:Phytohemagglutinins; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma