Comparison of CD3 and CD2 activation pathways in T cells from young and elderly adults.
The ability of purified T cells to be activated by immobilized anti-CD3 and soluble anti-CD2 monoclonal antibodies (mAbs) was compared using cells from young and old donors. Purified T cells from elderly humans activated with immobilized anti-CD3 mAb incorporated less [3H]thymidine (58,780 vs 92,258 cpm; p < 0.02) into cellular DNA, and secreted less IL-2 into the culture supernatants than did T cells from young donors. In contrast, T cells activated with anti-CD2 mAbs displayed no age-related differences in proliferation or IL-2 production. Anti-CD2 stimulation resulted in equal IL-2 synthesis by cells from young and old donors that was comparable to the amount produced by cells from elderly donors stimulated with immobilized anti-CD3. Northern blot analysis of early cell cycle gene expression by anti-CD2 activated T cells demonstrated no age differences in the expression of p55 IL-2R or c-myc specific mRNA, although T cells from elderly individuals activated with immobilized anti-CD3 showed statistically significant decreases in both mRNAs. T cell receptor beta chain mRNA levels did not differ between cells from young or old donors after activation by either anti-CD3 or anti-CD2. The discordance in proliferative ability, IL-2 secretion, and specific mRNA expression between T cells from elderly donors activated through the CD3-TCR complex or by soluble anti-CD2 mAbs provides additional evidence for a multifactorial causation of age-related T cell proliferative defects, and may indicate that the difference in proliferative ability is, in part, attributable to responsiveness to secreted IL-2.
Song
L J
LJ
Clinical Immunology Section, National Institute on Aging, NIH, Baltimore, MD 21224-2780.
Nagel
J E
JE
Chrest
F J
FJ
Collins
G D
GD
Adler
W H
WH
D000328:Adult; D000368:Aged; D000375:Aging / Q000276:immunology*; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D005260:Female; D015870:Gene Expression; D016259:Genes, myc; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2 / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D007376:Interleukin-2; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2