HETEROGENEOUS EFFECTS OF HISTAMINE ON PROLIFERATION OF LUNG-DERIVED AND BLOOD-DERIVED T-CELL CLONES FROM HEALTHY AND ASTHMATIC PERSONS

We have studied the effect of histamine on the proliferation and the intracellular cyclic adenosine monophosphate (cAMP) levels of T-lymphocyte clones (TLC) generated from bronchoalveolar lavage fluid (BALF) or peripheral blood (PB) from healthy and asthmatic persons. TLC from either compartment and from both groups of donors were heterogeneous in their response to histamine. In BALF-derived TLC, three types of responses were observed: histamine inhibited, stimulated, or did not modulate the anti-CD3-induced proliferation. Histamine directly and dose dependently inhibited the anti-CD3-induced proliferation of six (two asthmatic) of 12 CD4+ BALF TLC, stimulated two BALF TLC (both nonasthmatic), and did not modulate the proliferation of four BALF TLC. The maximal inhibition was 70%, the maximal stimulation 200%, both at 10(-3) M histamine. The stimulation of proliferation was associated with increased interleukin-2 (IL-2) production, whereas the inhibition of proliferation was associated with decreased IL-2 production and downregulation of IL-2 receptor expression. The inhibitory effects could be partly reversed by H-2-receptor antagonists and could be mimicked by an H-2-receptor agonist. In contrast, the stimulatory effect was not reversed or mimicked by H-1 or H-2 antagonists or agonists. The majority of CD4+ TLC responded to histamine with a rise in the intracellular cAMP levels. A rise in cAMP, however, was often but not always associated with an inhibition of proliferation. In addition, stimulation of proliferation occurred in the absence of a rise in cAMP. We compared cAMP rises in panels of TLC obtained with high cloning efficiencies from the PB from a healthy person and from an asthmatic person. There were no differences in basal levels between the two groups of TLC; however, CD4+ TLC from the asthmatic person as a group showed a lower histamine-induced cAMP rise than those from the healthy subject. The present results suggest that human CD4+ T cells are further subdivided in populations that differ phenotypically with respect to their response to histamine. The specific functional role of those subpopulations in the immune response remains to be clarified.