IL-6/BSF-2 selectively stimulates the GO----S progression of CD8+ lymphocytes.
IL-6 preferentially promotes the DNA synthesis of human peripheral blood CD8+, rather than CD4+, lymphocytes in presence of PHA: this effect is observed in serum-free cultures of greater than 99% purified CD8+ lymphocytes. However, IL-6 is able to stimulate DNA synthesis of CD8+ lymphocytes triggered by a mitogenic anti-CD2 mAb, but not by anti-CD3 mAb: these results suggest that IL-6 selectively induces activation of CD8+ lymphocytes through the CD2 rather than the CD3 pathway. Limiting dilution analysis indicates that accessory cells are not required to mediate the action of IL-6 on CD8+ cells. Furthermore, this action is not blocked by addition of mAb neutralizing either IL-2 or IL2R, thus suggesting that IL-6 does not act via IL-2. CD8+ lymphocytes grown in the presence of PHA + IL-6 incorporate (3H)-thymidine to the same extent as those stimulated with PHA + IL-2, but do not increase in number until day 6 of culture. It is hence apparent that the stimulating activity of IL-6 on CD8+ lymphocytes is restricted to the GO----S phase progression, but does not lead to mitosis. IL-6 receptors are expressed on resting CD4+ and CD8+ lymphocytes: their expression is significantly enhanced on both activated CD4+ and CD8+ cells. Scatchard analysis of (125I)-IL-6 binding data showed the presence of high (Kd, 3 x 10(-10) M) and low (Kd, 6 x 10(-8) M) affinity IL6R on both lymphocyte populations. Similarly, mRNA encoding IL6R was detected in both CD4+ and CD8+ lymphocytes. Thus, our studies indicate that IL-6 directly and selectively stimulates the GO----S progression of CD8+ lymphocytes in the presence of mitogen and absence of IL-2: this phenomenon may be of interest for the elucidation of mechanisms activating cytotoxic T lymphocytes.
Department of Hematology and Oncology, Istituto Superiore di Sanità, Roma, Italy.
D
D
Bulgarini
S
S
Scalzo
G
G
Boccoli
M
M
Petrini
M T
MT
Quaranta
A
A
Camagna
G
G
Isacchi
U
U
Testa
C
C
Peschle
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology; D015850:Interleukin-6 / Q000494:pharmacology*; D007399:Interphase; D008213:Lymphocyte Activation; D012333:RNA, Messenger; D011863:Radioimmunoassay; D011971:Receptors, Immunologic / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000276:immunology; D019947:Receptors, Interleukin-6; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D007376:Interleukin-2; D015850:Interleukin-6; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D019947:Receptors, Interleukin-6