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 i ntracellular cyclic adenosine monophosphate (cAMP) levels of T-lymphoc yte clones (TLC) generated from bronchoalveolar lavage fluid (BALF) or peripheral blood (PB) from healthy and asthmatic persons. TLC from ei ther compartment and from both groups of donors were heterogeneous in their response to histamine. In BALF-derived TLC, three types of respo nses were observed: histamine inhibited, stimulated, or did not modula te the anti-CD3-induced proliferation. Histamine directly and dose dep endently inhibited the anti-CD3-induced proliferation of six (two asth matic) of 12 CD4+ BALF TLC, stimulated two BALF TLC (both nonasthmatic ), and did not modulate the proliferation of four BALF TLC. The maxima l inhibition was 70%, the maximal stimulation 200%, both at 10(-3) M h istamine. The stimulation of proliferation was associated with increas ed interleukin-2 (IL-2) production, whereas the inhibition of prolifer ation was associated with decreased IL-2 production and downregulation of IL-2 receptor expression. The inhibitory effects could be partly r eversed by H-2-receptor antagonists and could be mimicked by an H-2-re ceptor agonist. In contrast, the stimulatory effect was not reversed o r 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 leve ls. A rise in cAMP, however, was often but not always associated with an inhibition of proliferation. In addition, stimulation of proliferat ion 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 f rom a healthy person and from an asthmatic person. There were no diffe rences in basal levels between the two groups of TLC; however, CD4+ TL C from the asthmatic person as a group showed a lower histamine-induce d cAMP rise than those from the healthy subject. The present results s uggest that human CD4+ T cells are further subdivided in populations t hat differ phenotypically with respect to their response to histamine. The specific functional role of those subpopulations in the immune re sponse remains to be clarified.