HLA class II molecules on monocytes regulate T cell proliferation through physical interaction in the CD3 activation pathway.
HLA class II molecules are involved in the OKT3-induced T cell activation, since monoclonal antibodies (mAb) to monomorphic determinants of class II antigens are able to inhibit T cell proliferation. This effect involves several of the events leading to T cell activation and proliferation, i.e. interleukin (IL) 1, IL 6 and IL2 secretion and IL2 receptor expression. The main target of the inhibition is represented by monocytes, and the interference of anti-class II mAb in the direct interaction of monocytes with T cells is likely to play a relevant role in the inhibition mechanism. To test this hypothesis, we investigated in the present study the effect of anti-class II mAb on the proliferation of T cells stimulated with mAb OKT3 in the presence of paraformaldehyde-treated monocytes. We show that the inhibition of proliferation is specific and dose dependent, and seems to involve particular class II epitopes. Addition of fixed monocytes to inhibited T cell cultures restores proliferation to a moderate extent, only if monocytes are added within the first 12 h of culture, suggesting that class II antigens or spatially related molecules deliver signals concurrently with the mitogenic stimulus. The blocking capability of anti-class II mAb was not restricted to the CD4+ or the CD8+ T cell subsets, suggesting that, under inhibitory conditions, these mAb affect other structures on the T cell surface, relevant to the monocyte-T cell interaction.
Ruggiero
G
G
Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II, Italy.
Racioppi
L
L
Manzo
C
C
Pirozzi
G
G
D'Oro
U
U
Ferrone
S
S
Zappacosta
S
S
Fontana
S
S
D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D017252:CD3 Complex; D015704:CD4 Antigens / Q000502:physiology; D006681:HLA-D Antigens / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007378:Interleukins / Q000494:pharmacology; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology*; D016853:Muromonab-CD3; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015704:CD4 Antigens; D006681:HLA-D Antigens; D007378:Interleukins; D016853:Muromonab-CD3; D011948:Receptors, Antigen, T-Cell