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Alternatively activated macrophages actively inhibit proliferation of peripheral blood lymphocytes and CD4 + T cells in vitro
Author(s) -
SCHEBESCH C.,
KODELJA V.,
MÜLLER C.,
HAKIJ N.,
BISSON S.,
ORFANOS C. E.,
GOERDT S.
Publication year - 1997
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1997.00371.x
Subject(s) - cd86 , phytohaemagglutinin , cd80 , microbiology and biotechnology , biology , in vitro , lymphocyte , antigen , concanavalin a , cd40 , immunology , t cell , cytotoxic t cell , immune system , biochemistry
We compared the immunological functions of interferon‐γ (IFN‐γ)‐induced, classically activated macrophages (caMΦ) and of interleukin‐4 (IL‐4)‐ and glucocorticoid‐induced, alternatively activated macrophages (aaMΦ) in a human co‐culture system in vitro . Proliferation of peripheral blood leucocytes (PBL) or CD4 + T cells mediated by optimal doses of phytohaemagglutinin (PHA) or concanavalin A (Con A) was only marginally influenced by caMΦ, but was strongly inhibited by aaMΦ. The degree of lymphocyte proliferation sustained in the presence of caMΦ was gradually reduced in a dose‐dependent fashion by the addition of aaMΦ. Flow cytometric analysis revealed that expression of costimulatory molecules such as CD11a, CD40, CD54, CD58, CD80 and CD86 did not vary significantly between caMΦ and aaMΦ and was low for CD58, CD80 and CD86. As shown by reverse transcriptase‐polymerase chain reaction (RT‐PCR) analysis, IL‐10 was expressed in caMΦ, aaMΦ and control macrophages; the level of expression of IL‐10 was slightly enhanced in aaMΦ. Neither neutralizing anti‐IL‐10 antibodies, indomethacin nor N G ‐monomethyl‐l‐arginine (NMMLA) was able to reverse aaMΦ‐mediated inhibition of lymphocyte proliferation. Of several agents interfering with various second messenger pathways, cAMP and the Ca 2+ ‐ionophor A23187 inhibited differentiation of cultured human monocytes into phenotypically mature aaMΦ expressing MS‐1 high molecular weight protein (MS‐1‐HMWP) and RM 3/1 antigen, and prevented the suppressive action of aaMΦ on lymphocyte proliferation. In conclusion, these results show that aaMΦ actively inhibit mitogen‐mediated proliferation of PBL and CD4 + T cells independently of the expression of costimulatory molecules and of IL‐10, NO or prostaglandin synthesis, and that inhibition of phenotypic differentiation of aaMΦ is paralleled by a lack of functional maturation. Thus, fully matured aaMΦ may be functional in down‐regulating CD4 + T‐cell‐mediated immune reactions by an as yet unknown mechanism.