T cell activation in the elderly: evidence for specific deficiencies in T cell/accessory cell interactions.
We studied T cell activation in the healthy aged (greater than 70 years) by examining lymphocyte proliferative responses to various mitogenic stimuli in accessory cell (AC)-dependent and AC-independent systems. Results show that despite a near normal response to the anti-CD3 monoclonal antibody (mAb) OKT3, peripheral blood mononuclear cells (PBM) from the elderly exhibit a profound reduction in phytohaemagglutinin (PHA)-responsiveness (approximately 30% of young adults). This deficit becomes even more severe at suboptimal doses of PHA. Adding exogenous interleukin-2 (IL-2) or pretreating the AC population with gamma interferon (IFN-gamma) returns the level of proliferation to that seen with young adults. Furthermore, replacing "old" AC with AC from young adults or with U937 (a monocytic cell line) in T cell/AC cell-mixing experiments restores PHA-responsiveness in 70% of cases. On the other hand, AC from the aged fully support PHA responses in T cells from young adults. In AC-depleted cultures, purified T cells from the aged respond normally to the co-mitogenic stimuli, PHA + PMA. Taken together, these results suggest that the age-associated diminution in PHA-responsiveness is due, at least in part, to specific deficiencies in T cell/AC communication.
Beckman
I
I
Department of Clinical Immunology, Flinders Medical Centre, Bedford Park, S.A.
Dimopoulos
K
K
Xu
X N
XN
Bradley
J
J
Henschke
P
P
Ahern
M
M
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000502:physiology*; D002450:Cell Communication; D002455:Cell Division / Q000502:physiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D010835:Phytohemagglutinins / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology*
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D010835:Phytohemagglutinins; D007371:Interferon-gamma