Costimulation by purified intercellular adhesion molecule 1 and lymphocyte function-associated antigen 3 induces distinct proliferation, cytokine and cell surface antigen profiles in human "naive" and "memory" CD4+ T cells.
Activation of resting human CD4+ "naive" (CD45RA+CD45RO-) and "memory" (CD45RA-CD45RO+) T cells requires costimulatory signals in addition to engagement of the T cell receptor/CD3 complex (TCR/CD3). The adhesion pathways mediated by lymphocyte function-associated antigen 1/intercellular adhesion molecule 1 (LFA-1/ICAM-1) and CD2/LFA-3 are capable of providing such costimulatory signals. Our work shows that these costimulatory adhesion pathways are critically involved in regulation of T cell differentiation/maturation. Evidence for subset-specific costimulatory requirements is demonstrated by the finding that only memory CD4+ T cells were costimulated by LFA-3, whereas both naive and memory CD4+ T cells were costimulated by ICAM-1. In addition, these costimulatory adhesion pathways regulated reciprocal cytokine secretion patterns for interleukin 5 (IL-5) and granulocyte/macrophage colony-stimulating factor (GM-CSF). Repeated costimulation of CD4+ memory T cells with LFA-3 led to secretion of high levels of IL-5, while repeated costimulation with ICAM-1 induced high levels of secreted GM-CSF. Significant interferon gamma (IFN-gamma) production was observed with either of the costimulatory ligands. Extensive cell surface analysis of these in vitro cultures of peripheral blood derived memory CD4+ T cells, with monoclonal antibodies obtained from the 5th Leucocyte Typing Workshop, revealed differential expression of a singular antigen, CD60. This antigen was preferentially expressed on LFA-3-costimulated cells suggesting a positive correlation between CD60 expression and a T helper type 2-like cytokine profile. In conclusion, this report demonstrates a new functional role for costimulatory adhesion molecules in regulating differential cytokine secretion in human memory CD4+ T cells.
Semnani
R T
RT
Department of Pathology, University of Chicago, Illinois 60637.
Nutman
T B
TB
Hochman
P
P
Shaw
S
S
van Seventer
G A
GA
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis* / Q000494:pharmacology*; D017252:CD3 Complex / Q000276:immunology / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018968:CD58 Antigens; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004347:Drug Interactions; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007156:Immunologic Memory; D018799:Intercellular Adhesion Molecule-1 / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000494:pharmacology; D015848:Interleukin-5 / Q000096:biosynthesis; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D017252:CD3 Complex; D018968:CD58 Antigens; D016207:Cytokines; D007376:Interleukin-2; D015848:Interleukin-5; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor