Elevation of intracellular cAMP in human T lymphocytes by an anti-CD44 mAb.
Regulation of lymphocyte responses to activation of the CD3/TCR complex by other cell surface proteins expressed on lymphocytes is a well established phenomenon. CD44 is an example of such a cell surface protein. Anti-CD44 mAb have been identified which either stimulate or inhibit lymphocyte function. Certain anti-CD44 mAb augment proliferation and IL-2 production by T cells stimulated through the CD2 or CD3/TCR pathways. An anti-CD44 mAb with opposing properties has also been identified. This mAb inhibits activation of human T cells by preventing the rise in [Ca2+]i stimulated by OKT3. The purpose of experiments reported here was to further characterize this phenomenon. The results show that the anti-CD44 mAb, 212.3, does not inhibit inositol phosphate turnover stimulated by OKT3 but does inhibit elevation of intracellular [Ca2+]i in these same cells. Addition of 212.3 to purified human T cells results in a rapid increase in intracellular levels of cAMP. Elevation of cAMP by 212.3 is time- and concentration-dependent. Activation of adenylate cyclase by forskolin also results in elevation of intracellular cAMP and inhibition of the increase in [Ca2+]i stimulated by OKT3. Taken together, these data suggest that CD44 may be positively coupled to adenylate cyclase and that activation of adenylate cyclase by the anti-CD44 mAb, 212.3, may mediate the inhibition of the OKT3-stimulated elevation of [Ca2+]i.
Rothman
B L
BL
Institute of Arthritis and Autoimmunity, Miles Research Center, West Haven, CT 06516.
Kennure
N
N
Kelley
K A
KA
Katz
M
M
Aune
T M
TM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D018801:CD2 Antigens; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors; D007295:Inositol Phosphates / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D016853:Muromonab-CD3 / Q000276:immunology; D011971:Receptors, Immunologic / Q000502:physiology; D016201:Receptors, Lymphocyte Homing / Q000276:immunology / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D018960:Hyaluronan Receptors; D007295:Inositol Phosphates; D016853:Muromonab-CD3; D011971:Receptors, Immunologic; D016201:Receptors, Lymphocyte Homing; D005576:Colforsin; D000242:Cyclic AMP; D002118:Calcium