Cooperation between an anti-T cell (anti-CD28) monoclonal antibody and monocyte-produced IL-6 in the induction of T cell responsiveness to IL-2.
CD28 is an Ag of 44-kDa Mr that is expressed on the membrane of the majority of human T cells and that is recognized by mAb 9.3. The functional effects of mAb 9.3 on peripheral blood T cells were studied. mAb 9.3 was not mitogenic, unless it was combined with PMA. When CD28 was cross-linked after binding of mAb 9.3 to the T cell by immobilized or soluble anti-mouse IgG, T cells proliferated in response to rIL-2, provided that monocytes were also present. The additional signal required for IL-2 responsiveness after cross-linking of CD28 could also be delivered in cultures of purified T cells by a cellfree monocyte culture supernatant. Expression of IL-2R on about 10% of the T cells was demonstrated by staining with an anti-IL-2R mAb, and was found to be largely restricted to CD4+ cells. The active compound responsible for the helper signal in the monocyte culture supernatant was identified as IL-6 because purified IL-6 (but not IL-1 beta) had similar activity and because an antiserum to IL-6 (but not an antiserum to IL-1 beta) neutralized the activity of the monocyte supernatant and blocked T cell proliferation. An anti-IL-2R antibody also completely inhibited T cell proliferation induced by the combination of mAb 9.3, IL-2, and IL-6. Our results provide evidence that cross-linking of CD28 induces functional IL-2R and that this activity is dependent on a helper signal provided by monocytes, more specifically IL-6. Moreover, our results indicate that IL-6 (previously called B cell stimulatory factor-2) is active on T cells. If a natural ligand for CD28 can be identified, the mechanism of induction of IL-2 responsiveness described here might explain how T cells become nonspecifically involved in an ongoing cellular immune reaction.
Baroja
M L
ML
Department of Medicine and Pathophysiology, University of Leuven, Belgium.
Ceuppens
J L
JL
Van Damme
J
J
Billiau
A
A
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000328:Adult; D000911:Antibodies, Monoclonal / Q000502:physiology*; D000938:Antigen-Presenting Cells / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte; D002474:Cell-Free System; D002478:Cells, Cultured; D003432:Cross-Linking Reagents; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D015850:Interleukin-6; D007378:Interleukins / Q000096:biosynthesis* / Q000502:physiology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D003432:Cross-Linking Reagents; D007376:Interleukin-2; D015850:Interleukin-6; D007378:Interleukins